Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new...Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.展开更多
Converting CO_(2) into valuable chemicals is an effective means to alleviate environmental pressure and the depletion of oil resources.Among them,polymers derived from the copolymerization of PO and CO_(2) have been w...Converting CO_(2) into valuable chemicals is an effective means to alleviate environmental pressure and the depletion of oil resources.Among them,polymers derived from the copolymerization of PO and CO_(2) have been widely studied because of their excellent properties.To meet the expansion of the application range of CO_(2)-based polymers,regulation of the CU in the polymer is imperative.Based on the understanding of the relationship between catalyst synergy and structure,we designed a new generation of polyester-based polymeric catalysts APEPC-R and RPEPC-N with discretely distributed active centers to achieve the synthesis of CO_(2)-based polymers with regulated CU(from 50%to 90%).The discrete arrangement of catalyst active centers was demonstrated by 1H NMR and UV-vis characterization.Benefiting from multi-site synergy,high molecular weight(M_(n)>100 kg/mol)CO_(2)-based copolymers with CU among 50%—90%were successfully synthesized and their properties were firstly investigated.This work not only contributes to enriching the scope of the application of CO_(2)-based copolymers but also provides a new platform for the development of a new generation of catalysts.展开更多
It is of great interest to make a degradable material widely tailorable to replace petroleum-derived products among diverse applications.Here,we report the construction of a new multi-purpose degradable material for t...It is of great interest to make a degradable material widely tailorable to replace petroleum-derived products among diverse applications.Here,we report the construction of a new multi-purpose degradable material for the first time via a simple ternary copolymerization system comprisingε-caprolactone(ε-CL),cyclohexane oxide(CHO)and CO_(2).Under low pressure of 1 bar∼5 bar,the ring-opening polymerization(ROP)ofε-CL and ring-opening copolymerization(ROCOP)of CO_(2) and CHO can simultaneously proceed.The carbonate units are randomly distributed on the polymer chain.These random terpolymers have controllable molar mass(10-106 kDa)and compositions(4-33 mol%CO_(2)).And the obtained materials show large-span tunability from tough plastic to elastomer and even adhesive.展开更多
A new strategy for the metal-free coordination–insertion ring-opening polymerization of tetrahydrofuran by the central metalloid Boron has been first identified.Bis(pentafluorophenyl)(phenoxy)borane was used as a cat...A new strategy for the metal-free coordination–insertion ring-opening polymerization of tetrahydrofuran by the central metalloid Boron has been first identified.Bis(pentafluorophenyl)(phenoxy)borane was used as a catalyst for the polymerization reaction system.And polytetrahydrofuran with high molecular weight and narrow molecular weight distribution could be obtained.The proposed mechanism was studied by MALDI-TOF,ESI-MS and O-18 isotope labeling analyses as a metal-free coordination insertion mechanism.展开更多
Biomedical materials represent a broad and important branch in material sciences and industry.Although the total mass is not quite high as other industrial materials,the added values are much higher.Specially,as an in...Biomedical materials represent a broad and important branch in material sciences and industry.Although the total mass is not quite high as other industrial materials,the added values are much higher.Specially,as an interdisciplinary subject,biomedical materials experienced a rapid development in the past few years as the progress in related subjects like biology,medicine and engineering.The current special topic titled“Biomedical Materials”aims to highlight the latest innovations,challenges,and opportunities in this exciting field.展开更多
In the version of the article originally published in the volume 66,issue 7,2023 of Sci China Mater(pages 2925–2937,https://doi.org/10.1007/s40843-022-2409-4),the images reported in Fig.2d showing the resulting cell ...In the version of the article originally published in the volume 66,issue 7,2023 of Sci China Mater(pages 2925–2937,https://doi.org/10.1007/s40843-022-2409-4),the images reported in Fig.2d showing the resulting cell morphologies after incubation with PPAH at the concentrations of 0,125,and 250μg mL^(−1)were misused.The corrected Fig.2 is given below.These corrections do not change or affect the results or conclusions of the paper.展开更多
We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity.When we conjugated a series of five-,six-,or seven-membered heterocyclic molecu...We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity.When we conjugated a series of five-,six-,or seven-membered heterocyclic molecules to branched polyethylenimine(bPEI),over 70%of them could induce the secretion of interferon-β(IFN-β)from murine dendritic and human leukemia monocytic(DC2.4 and THP-1)cells through activating the stimulator of interferon genes(STING)pathway.We further proved that this kind of innate stimulating activity was dependent on the macromolecular architecture as heterocyclic molecules tethered linear PEI(lPEI)or dendritic polyamidoamine(PAMAM)induced no or much less IFN-βsecretion.Furthermore,we prepared a series of poly-L-lysine(PLL)-derivatives with different branches to tether with heterocyclic molecules and proved that this kind of bPEI-like structure was important in en hancing the binding affinity with STING proteins and for exhibiting innate stimulating activity.展开更多
Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the...Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.展开更多
Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, ...Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.展开更多
Cell-material and cell-cell interactions represent two crucial aspects of the regulation of cell behavior.In the present study,poly(L-glutamic acid)(PLG)hydrogels were prepared by catalyst-free click crosslinking via ...Cell-material and cell-cell interactions represent two crucial aspects of the regulation of cell behavior.In the present study,poly(L-glutamic acid)(PLG)hydrogels were prepared by catalyst-free click crosslinking via a strain-promoted azide-alkyne cycloaddition(SPAAC)reaction between azido-grafted PLG(PLG-N3)and azadibenzocyclooctyne-grafted PLG(PLG-ADIBO).The bioactive peptides c(RGDfK)and N-cadherin mimetic peptide(N-Cad)were both conjugated to the PLG hydrogel(denoted PLG+RGD/N-Cad)in order to regulate cell-material and cell-cell interactions.Gelation time and storage modulus of the hydrogels were tunable through variations in the concentration of polypeptide precursors.The hydrogels degraded gradually in the presence of proteinases.The viability of bone marrow mesenchymal stem cells(BMSCs)was maintained when cultured with extracts of the hydrogels or encapsulated within the hydrogels.Degradation was observed within 10 weeks following the subcutaneous injection of hydrogel solution in rats,displaying excellent histocompatibility in vivo.The introduction of RGD into the PLG hydrogel promoted the adhesion of BMSCs onto the hydrogels.Moreover,when encapsulated within the PLG+RGD/NCad hydrogel,BMSCs secreted cartilage-specific matrix,in addition to chondrogenic gene and protein expression being significantly enhanced in comparison with BMSCs encapsulated in hydrogels without N-Cad modification.These findings suggest that these biodegradable,bioactive polypeptide hydrogels have great potential for use in 3D cell culture and in cartilage tissue engineering.展开更多
Melanoma has been a serious threat to the human health;however,effective therapeutic methods of this cancer are still limited.Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy.I...Melanoma has been a serious threat to the human health;however,effective therapeutic methods of this cancer are still limited.Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy.In this paper,a chemo-immunotherapy system of DOX,IL-2 and IFN-g based on poly(g-ethyl-Lglutamate)-poly(ethylene glycol)-poly(g-ethyl-L-glutamate)(PELG-PEG-PELG)hydrogel was developed for local treatment of melanoma xenograft.The drug release process of this system exhibited a short term of burst release(the first 3 days),followed by a long-term sustained release(the following 26 days).The hydrogel degraded completely within 3 weeks without obvious inflammatory responses in the subcutaneous layer of rats,showing a good biodegradability and biocompatibility.The DOX/IL-2/IFN-g co-loaded hydrogel also showed enhanced anti-tumor effect against B16F10 cells in vitro,through increasing the ratio of cell apoptosis and G2/S phage cycle arrest.Moreover,the combined strategy presented improved therapy efficacy against B16F10 melanoma xenograft without obvious systemic side effects in a nude mice model,which was likely related to both the enhanced tumor cell apoptosis and the increased proliferation of the CD3t/CD4t T-lymphocytes and CD3t/CD8t T-lymphocytes.Overall,the strategy of localized co-delivery of DOX/IL-2/IFN-g using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy.展开更多
Many conventional chemotherapeutics play an immune-modulating effect by inducing immunogenic cell death(ICD)in tumor cells.However,they hardly arouse strong antitumor immune response because the immunosuppressive lymp...Many conventional chemotherapeutics play an immune-modulating effect by inducing immunogenic cell death(ICD)in tumor cells.However,they hardly arouse strong antitumor immune response because the immunosuppressive lymphocytes are present in the tumor microenvironment.These immunosuppressive lymphocytes include regulatory T cells(Tregs)and myeloid-derived suppressor cells(MDSCs).We used a low dose of doxorubicin(DOX)to induce ICD in combination with immune regulator 1-methylDL-tryptophan(1 MT)to suppress indoleamine 2,3-dioxygenase and overcome Treg-and MDSCassociated immune suppression.By co-encapsulation of DOX and 1 MT into a reduction-responsive polypeptide nanogel,the drugs were simultaneously released in the tumor cells and synergistically performed antitumor efficacy.After treatment,recruitment of Tregs and MDSCs was inhibited,and the frequency of tumor-infiltrating CD8+T cells was remarkably enhanced.These results demonstrated that the chemoimmunotherapy strategy effectively suppressed tumor growth without causing evident adverse effects,indicating its great potential in clinical cancer therapy.展开更多
Osteosarcoma is the most common malignancy in the bone. Current chemotherapy offers limited efficacy with significant side effects, especially for advanced and relapsed osteosarcomas. Nanoparticle-formulated chemother...Osteosarcoma is the most common malignancy in the bone. Current chemotherapy offers limited efficacy with significant side effects, especially for advanced and relapsed osteosarcomas. Nanoparticle-formulated chemotherapeutic drugs may be used to resolve these issues, but several aspects of these formulations remain unsatisfactory, such as how to improve their stability in the bloodstream, prevent undesirable drug leakage, and enhance targeted drug accumulation in the tumor. In this study, a tumor microenvironment-responsive calcium carbonate （CaCO3）- crosslinked hyaluronate （HA） nanopartide was prepared via a ＂green＂ process to effectively deliver doxorubicin （DOX） for the treatment of various stages of osteosarcoma. The DOX-loaded hyaluronate-calcium carbonate hybrid nanoparfide （HA-DOX/CaCO3） demonstrated superior stability both in vitro and in vivo, and rapidly released DOX at the tumor site when triggered by the acidic tumor microenvironment. Compared with free DOX and a non-crosslinked nanoparficle （HA-DOX）, HA-DOX]CaCO3 exhibited the most potent inhibition efficacy toward both primary and advanced models of routine osteosarcoma, resulting in effective tumor inhibition, improved survival time, and reduced adverse effects. Most importantly, in the advanced osteosarcoma model, HA-DOX/CaCO3 potently suppressed tumor growth by 84.6%, which indicates the potential of this platform for osteosarcoma treatment, particularly for advanced and relapsed cases. The proposed polysaccharide nanopartide would be a promising drug delivery platform to advance osteosarcoma nanomedicine.展开更多
Mesoporous nano-hydroxyapatite （n-HA） has gained more and more attention as drug storage and release hosts. The aim of this study is to observe the effect of the ratio of surfactant to the theoretical yield of HA on...Mesoporous nano-hydroxyapatite （n-HA） has gained more and more attention as drug storage and release hosts. The aim of this study is to observe the effect of the ratio of surfactant to the theoretical yield of HA on the mesoporous n-HA, then to reveal the effect of the mesoporous nanostructure on protein delivery. The mesoporous n-HA was synthesized using the wet precipitation in the presence of cetyltrimethylammonium bromide （CTAB） at ambient temperature and normal atmospheric pressure. The morphology, size, crystalline phase, chemical composition and textural characteristics of the product were well characterized by X-ray Powder Diffraction （XRD）, Fourier Transform Infrared Spectroscopy （FTIR）, Scanning Electron Microscopy （SEM）, Transmission Electron Microscopy （TEM）, Dynamic Light Scattering （DLS） and N2 adsorption/desorption, respectively. The protein adsorption/release studies were also carried out by using Bovine Serum Albumin （BSA） as a model protein. The results reveal that the mesoporous n-HA synthesized with CTAB exhibits high pure phase, low crystallinity and the typical characteristics of the mesostructure. The BSA loading increases with the specific surface area and the pore volume of n-HA, and the release rates of BSA are different due to their different pore sizes and pore structures, n-HA synthesized with 0.5% CTAB has the highest BSA loading and the slowest release rate because of its highest surface area and smaller pore size. These mesoporous n-HA materials demonstrate a potential application in the field of protein delivery due to their bioactive, biocompatible and mesoporous properties.展开更多
In order to architecturally and functionally mimic native Extracellular Matrix （ECM）, a novel micro/nano-fibrous scaffold of hydroxyapetite/poly（lactide-co-glycolide） （HA/PLGA） composite was successfully prepare...In order to architecturally and functionally mimic native Extracellular Matrix （ECM）, a novel micro/nano-fibrous scaffold of hydroxyapetite/poly（lactide-co-glycolide） （HA/PLGA） composite was successfully prepared by melt-spinning method. A porous three-dimensional scaffold fabricated by melt-molding particulate-leaching method was used as control. This kind of scaffold comprising both nanofiber and microfiber had an original structure including a nano-network favorable for cell adhe- sion, and a micro-fiber providing a strong skeleton for support. The microfibers and nanofibers were blended homogeneously in scaffold and the compression strength reached to 6.27 MPa, which was close to human trabecular bone. The typical mi- cro/nano-fibrous structure was more benefcial for the proliferation and differentiation of Bone Mesenehymal Stem Cells （BMSCs）. The calcium deposition and Alkaline Phosphatase （ALP） activity were evaluated by the differentiation of BMSCs, and the results indicated that the temporary ECM was very beneficial for the differentiation of BMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, micro/nano-fibrous scaffold was used for the purpose of rapid bone remodeling in the defect area. The results showed that a distinct bony callus of bridging was observed at 12 weeks post-surgery and the expression of osteogenesis-related genes （bone-morphogenetic protein-2, Osteonectin, collagen-I） increased because of the ECM-like structure. Based on the results, the novel micro/nano-fibrous scaffold might be a promising candidate for bone tissue engi- neering.展开更多
Intravesical chemotherapy has been recommended after the gold standard of transurethral resection of the bladder tumor to prevent bladder cancer(BC)from local recurrence in the clinic.However,due to rapid urine excret...Intravesical chemotherapy has been recommended after the gold standard of transurethral resection of the bladder tumor to prevent bladder cancer(BC)from local recurrence in the clinic.However,due to rapid urine excretion and barrier protection of the bladder wall,the clinical performances of chemotherapeutic drugs are severely compromised.In the present work,a smart positively charged disulfide-crosslinked nanogel of oligoarginine-poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine)(R_(9)-PEG-P(LP-co-LC))was prepared to prolong the retention period and enhance the penetration capability of chemotherapeutic agent toward the bladder wall.PEG significantly improved the aqueous dispersibility of the 10-hydroxycamptothecin(HCPT)-loaded R_(9)-PEG-P(LP-co-LC)(i.e.,R_(9)NG/HCPT)and enhanced the mucoadhesive capability by the nonspecific interaction between PEG chain and the bladder mucosa accompanied with the electrostatic interaction between the cationic R_(9)and negatively charged bladder mucosa.Besides,R_(9),as a cell-penetrating peptide,efficiently penetrated through the cell membrane and delivered carried cargo.The disulfide bond endowed the selective release behavior of HCPT triggered by the intracellular reductive microenvironment.As an advanced chemotherapeutic nanoformulation,the smart R_(9)NG/HCPT demonstrated superior cytotoxicity against human BC 5637 cells in vitro and remarkably enhanced tumor suppression activity toward orthotopic BC models of mouse and rat in vivo,indicating its great potential in the clinical intravesical BC chemotherapy.展开更多
Tumor nanovaccines have potential applications in the prevention and treatment of malignant tumors.However,it remains a longstanding challenge in exploiting efficient nanocarriers for inducing potent specifically cell...Tumor nanovaccines have potential applications in the prevention and treatment of malignant tumors.However,it remains a longstanding challenge in exploiting efficient nanocarriers for inducing potent specifically cellular immune responses.Toward this objective,we herein explore an intensive tumor immunotherapeutic strategy by combining mannosylated nanovaccines and gene regulated PD-L1 blockade for immune stimulation and killing activity.Here,we fabricate a mannose modified PLL-RT(Man-PLL-RT)mediated nanovaccines with dendritic cells(DCs)targeting capacity.Man-PLL-RT is capable of co-encapsulating with antigen(ovalbumin,OVA)and adjuvant(unmethylated cytosine-phosphate-guanine,CpG)by electrostatic interaction.This positively charged Man-PLL-RT/OVA/CpG nanovaccines can facilitate the endocytosis,maturation and cross presentation in DCs.However,the nanovaccines arouse limited inhibition of tumor growth,which is mainly due to the immunosuppressed microenvironment of tumors.Combining tumor nanovaccines with gene regulated PD-L1 blockade leads to an obvious tumor remission in B16F10 melanoma bearing mice.The collaborative strategy provides essential insights to boost the benefits of tumor vaccines by regulating the checkpoint blockade with gene therapy.展开更多
Despite of the promising achievements of immune checkpoints blockade therapy(ICB) in the clinic,which was often limited by low objective responses and severe side effects.Herein,we explored a synergistic strategy to c...Despite of the promising achievements of immune checkpoints blockade therapy(ICB) in the clinic,which was often limited by low objective responses and severe side effects.Herein,we explored a synergistic strategy to combine in situ vaccination and gene-mediated anti-PD therapy,which was generated by unmethylated cytosine-phosphate-guanine(CpG) and pshPD-L1 gene co-delivery.PEI worked as the delivery carrier to co-deliver the CpG and pshPD-L1 genes,the formed PDC(PEI/DNA/CpG)nanoparticles were further shielded by aldehyde modified polyethylene glycol(OHC-PEG-CHO) via pH responsive Schiff base reaction for OHC-PEG-CHO-PEI/DNA/CpG nanoparticles(P(PDC) NPs) prepa ration.All steps could be finished within 30 min.Such simple nanoparticles achieved the synergistic antitumor efficacy in B16 F10 tumor-bearing mice,and the amplified T cell responses,together with enhanced NK cells infiltration were observed after the combined treatments.In addition,the pH responsive delivery system reduced the side effects triggered by anti-PD therapy.The facile and effective combination strategy we presented here might provide a novel treatment for tumor inhibition.展开更多
The osteochondral defects caused by vigorous trauma or physical disease are difficult to be managed.Tissue engineering provides a possible option to regenerate the damaged osteochondral tissues.For osteochondral recon...The osteochondral defects caused by vigorous trauma or physical disease are difficult to be managed.Tissue engineering provides a possible option to regenerate the damaged osteochondral tissues.For osteochondral reconstruction,one intact scaffold should be considered to support the regeneration of both cartilage and subchondral bone.Therefore,the biphasic scaffolds with the mimic structures of osteochondral tissues have been developed to close this chasm.A variety of biomimetic bilayer scaffolds fabricated from natural or synthetic polymers,or the ones loading with growth factors,cells,or both of them make great progresses in osteochondral defect repair.In this review,the preparation and in vitro and/or in vivo verification of bioinspired biphasic scaffolds are summarized and discussed,as well as the prospect is predicted.展开更多
Polypeptides are one kind of promising biodegradable and biocompatible biomedical polymers with the structural units of various a-amino acids.Polypeptides were first polymerized by the ring-opening polymerization(ROP)...Polypeptides are one kind of promising biodegradable and biocompatible biomedical polymers with the structural units of various a-amino acids.Polypeptides were first polymerized by the ring-opening polymerization(ROP)of α-amino acid N-carboxyanhydrides(NCAs)by Leuchs and Hermann in 1906.In the past decades,several effective strategies,including the selection of initiators,the adjustment of reaction conditions,and the introduction of catalysts,have been reported to improve the controllability of the ROP of various a-amino acid NCAs to synthesize different polypeptides with precise chemical structures and low polydispersity indexes.In this Review,the strategies,mechanisms,challenges,and opportunities for controlled synthesis of polypeptides by the ROP of differentα-amino acid NCAs have been declared.展开更多
基金supported by the national key R&D program(2022YFC2402703).
文摘Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.
基金financial support from the National Key Research and Development Program of China(No.2021YFD1700700)National Natural Science Foundation of China(Nos.51988102,22271275,22101277)Youth Innovation Promotion Association of Chinese Academy of Sciences(2023236).
文摘Converting CO_(2) into valuable chemicals is an effective means to alleviate environmental pressure and the depletion of oil resources.Among them,polymers derived from the copolymerization of PO and CO_(2) have been widely studied because of their excellent properties.To meet the expansion of the application range of CO_(2)-based polymers,regulation of the CU in the polymer is imperative.Based on the understanding of the relationship between catalyst synergy and structure,we designed a new generation of polyester-based polymeric catalysts APEPC-R and RPEPC-N with discretely distributed active centers to achieve the synthesis of CO_(2)-based polymers with regulated CU(from 50%to 90%).The discrete arrangement of catalyst active centers was demonstrated by 1H NMR and UV-vis characterization.Benefiting from multi-site synergy,high molecular weight(M_(n)>100 kg/mol)CO_(2)-based copolymers with CU among 50%—90%were successfully synthesized and their properties were firstly investigated.This work not only contributes to enriching the scope of the application of CO_(2)-based copolymers but also provides a new platform for the development of a new generation of catalysts.
基金funded by the National Key R&D Program of China(No.2021YFA1501700)the Science and Technology Development Plan of Jilin Province(Nos.20230101042JC,20210201059GX)+2 种基金the National Natural Science Foundation of China,Basic Science Center Program(No.51988102)the National Natural Science Foundation of China(Nos.52203017,52073272 and 22293062)Bureau of International Cooperation Chinese Academy of Sciences(No.029GJHZ2023017MI).
文摘It is of great interest to make a degradable material widely tailorable to replace petroleum-derived products among diverse applications.Here,we report the construction of a new multi-purpose degradable material for the first time via a simple ternary copolymerization system comprisingε-caprolactone(ε-CL),cyclohexane oxide(CHO)and CO_(2).Under low pressure of 1 bar∼5 bar,the ring-opening polymerization(ROP)ofε-CL and ring-opening copolymerization(ROCOP)of CO_(2) and CHO can simultaneously proceed.The carbonate units are randomly distributed on the polymer chain.These random terpolymers have controllable molar mass(10-106 kDa)and compositions(4-33 mol%CO_(2)).And the obtained materials show large-span tunability from tough plastic to elastomer and even adhesive.
基金funded by the National Key R&D Program of China(No.2021YFA1501700)the Science and Technology Development Plan of Jilin Province(Nos.20230101042JC,20210201059GX)+2 种基金the National Natural Science Foundation of China,Basic Science Center Program(No.51988102)the National Natural Science Foundation of China(Nos.52203017,52073272 and 22293062)Bureau of International Cooperation Chinese Academy of Sciences(No.029GJHZ2023017MI)。
文摘A new strategy for the metal-free coordination–insertion ring-opening polymerization of tetrahydrofuran by the central metalloid Boron has been first identified.Bis(pentafluorophenyl)(phenoxy)borane was used as a catalyst for the polymerization reaction system.And polytetrahydrofuran with high molecular weight and narrow molecular weight distribution could be obtained.The proposed mechanism was studied by MALDI-TOF,ESI-MS and O-18 isotope labeling analyses as a metal-free coordination insertion mechanism.
文摘Biomedical materials represent a broad and important branch in material sciences and industry.Although the total mass is not quite high as other industrial materials,the added values are much higher.Specially,as an interdisciplinary subject,biomedical materials experienced a rapid development in the past few years as the progress in related subjects like biology,medicine and engineering.The current special topic titled“Biomedical Materials”aims to highlight the latest innovations,challenges,and opportunities in this exciting field.
文摘In the version of the article originally published in the volume 66,issue 7,2023 of Sci China Mater(pages 2925–2937,https://doi.org/10.1007/s40843-022-2409-4),the images reported in Fig.2d showing the resulting cell morphologies after incubation with PPAH at the concentrations of 0,125,and 250μg mL^(−1)were misused.The corrected Fig.2 is given below.These corrections do not change or affect the results or conclusions of the paper.
基金the Bureau of International Cooperation Chinese Academy of Sciences(grant no.121522KYSB20200029)National Natural Science Foundation of China(grant nos.22222509,52025035,52003268,and 51973215)+3 种基金Jilin Province Science and Technology Development Plan(grant nos.YDZJ202101-ZYTS131 and 20220402037GH)Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers(grant no.20210504001GH)Changchun Science and Technology Development Plan(grant no.21ZY09)the Youth Innovation Promotion Association of Chinese Academy of Sciences(grant no.2020232).
文摘We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity.When we conjugated a series of five-,six-,or seven-membered heterocyclic molecules to branched polyethylenimine(bPEI),over 70%of them could induce the secretion of interferon-β(IFN-β)from murine dendritic and human leukemia monocytic(DC2.4 and THP-1)cells through activating the stimulator of interferon genes(STING)pathway.We further proved that this kind of innate stimulating activity was dependent on the macromolecular architecture as heterocyclic molecules tethered linear PEI(lPEI)or dendritic polyamidoamine(PAMAM)induced no or much less IFN-βsecretion.Furthermore,we prepared a series of poly-L-lysine(PLL)-derivatives with different branches to tether with heterocyclic molecules and proved that this kind of bPEI-like structure was important in en hancing the binding affinity with STING proteins and for exhibiting innate stimulating activity.
基金supported by the National Natural Science Foundation of China (11621505, 11435002, 31671016)
文摘Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations.
基金supported by the National Natural Science Foundation of China (52073218, 22135005, 51873162, 51933006,51988102, 52122310, 22075050, 51833008, 51733006, 51733001,52122304)Jiangsu Province Science Foundation for Youths(BK20200241)+3 种基金Science and Technology Commission of Shanghai Municipality (20JC1414902, 21511104900)Shanghai Municipal Education Commission (2017-01-07-00-07-E00062)the National Key Research and Development Program (2021YFA1201200) of Chinathe Zhejiang Provincial Key Research and Development Program (2020C01123)。
文摘Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy. Furthermore, the foreseeable challenges and outlook of the development of more efficient, healthier and safer biomedical polymers are discussed. We wish this systemic and comprehensive review on highlighting frontier progress of biomedical polymers could inspire and promote new breakthrough in fundamental research and clinical translation.
基金supported by the National Natural Science Foundation of China(51973218,51622307,21574127,51520105004)the Youth Innovation Promotion Association,Chinese Academy of Sciences。
文摘Cell-material and cell-cell interactions represent two crucial aspects of the regulation of cell behavior.In the present study,poly(L-glutamic acid)(PLG)hydrogels were prepared by catalyst-free click crosslinking via a strain-promoted azide-alkyne cycloaddition(SPAAC)reaction between azido-grafted PLG(PLG-N3)and azadibenzocyclooctyne-grafted PLG(PLG-ADIBO).The bioactive peptides c(RGDfK)and N-cadherin mimetic peptide(N-Cad)were both conjugated to the PLG hydrogel(denoted PLG+RGD/N-Cad)in order to regulate cell-material and cell-cell interactions.Gelation time and storage modulus of the hydrogels were tunable through variations in the concentration of polypeptide precursors.The hydrogels degraded gradually in the presence of proteinases.The viability of bone marrow mesenchymal stem cells(BMSCs)was maintained when cultured with extracts of the hydrogels or encapsulated within the hydrogels.Degradation was observed within 10 weeks following the subcutaneous injection of hydrogel solution in rats,displaying excellent histocompatibility in vivo.The introduction of RGD into the PLG hydrogel promoted the adhesion of BMSCs onto the hydrogels.Moreover,when encapsulated within the PLG+RGD/NCad hydrogel,BMSCs secreted cartilage-specific matrix,in addition to chondrogenic gene and protein expression being significantly enhanced in comparison with BMSCs encapsulated in hydrogels without N-Cad modification.These findings suggest that these biodegradable,bioactive polypeptide hydrogels have great potential for use in 3D cell culture and in cartilage tissue engineering.
基金The financial support from the National Natural Science Foundation of China(No.51403202,51622307,51390484,51520105004)are gratefully thanked.
文摘Melanoma has been a serious threat to the human health;however,effective therapeutic methods of this cancer are still limited.Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy.In this paper,a chemo-immunotherapy system of DOX,IL-2 and IFN-g based on poly(g-ethyl-Lglutamate)-poly(ethylene glycol)-poly(g-ethyl-L-glutamate)(PELG-PEG-PELG)hydrogel was developed for local treatment of melanoma xenograft.The drug release process of this system exhibited a short term of burst release(the first 3 days),followed by a long-term sustained release(the following 26 days).The hydrogel degraded completely within 3 weeks without obvious inflammatory responses in the subcutaneous layer of rats,showing a good biodegradability and biocompatibility.The DOX/IL-2/IFN-g co-loaded hydrogel also showed enhanced anti-tumor effect against B16F10 cells in vitro,through increasing the ratio of cell apoptosis and G2/S phage cycle arrest.Moreover,the combined strategy presented improved therapy efficacy against B16F10 melanoma xenograft without obvious systemic side effects in a nude mice model,which was likely related to both the enhanced tumor cell apoptosis and the increased proliferation of the CD3t/CD4t T-lymphocytes and CD3t/CD8t T-lymphocytes.Overall,the strategy of localized co-delivery of DOX/IL-2/IFN-g using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy.
基金supported by the National Natural Science Foundation of China(51973216,51873207,51803006,51833010,51673190,and 51603204)the Science and Technology Development Program of Jilin Province(20200404182YY)+1 种基金the Youth Talents Promotion Project of Jilin Province(181909)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2019005)。
文摘Many conventional chemotherapeutics play an immune-modulating effect by inducing immunogenic cell death(ICD)in tumor cells.However,they hardly arouse strong antitumor immune response because the immunosuppressive lymphocytes are present in the tumor microenvironment.These immunosuppressive lymphocytes include regulatory T cells(Tregs)and myeloid-derived suppressor cells(MDSCs).We used a low dose of doxorubicin(DOX)to induce ICD in combination with immune regulator 1-methylDL-tryptophan(1 MT)to suppress indoleamine 2,3-dioxygenase and overcome Treg-and MDSCassociated immune suppression.By co-encapsulation of DOX and 1 MT into a reduction-responsive polypeptide nanogel,the drugs were simultaneously released in the tumor cells and synergistically performed antitumor efficacy.After treatment,recruitment of Tregs and MDSCs was inhibited,and the frequency of tumor-infiltrating CD8+T cells was remarkably enhanced.These results demonstrated that the chemoimmunotherapy strategy effectively suppressed tumor growth without causing evident adverse effects,indicating its great potential in clinical cancer therapy.
文摘Osteosarcoma is the most common malignancy in the bone. Current chemotherapy offers limited efficacy with significant side effects, especially for advanced and relapsed osteosarcomas. Nanoparticle-formulated chemotherapeutic drugs may be used to resolve these issues, but several aspects of these formulations remain unsatisfactory, such as how to improve their stability in the bloodstream, prevent undesirable drug leakage, and enhance targeted drug accumulation in the tumor. In this study, a tumor microenvironment-responsive calcium carbonate （CaCO3）- crosslinked hyaluronate （HA） nanopartide was prepared via a ＂green＂ process to effectively deliver doxorubicin （DOX） for the treatment of various stages of osteosarcoma. The DOX-loaded hyaluronate-calcium carbonate hybrid nanoparfide （HA-DOX/CaCO3） demonstrated superior stability both in vitro and in vivo, and rapidly released DOX at the tumor site when triggered by the acidic tumor microenvironment. Compared with free DOX and a non-crosslinked nanoparficle （HA-DOX）, HA-DOX]CaCO3 exhibited the most potent inhibition efficacy toward both primary and advanced models of routine osteosarcoma, resulting in effective tumor inhibition, improved survival time, and reduced adverse effects. Most importantly, in the advanced osteosarcoma model, HA-DOX/CaCO3 potently suppressed tumor growth by 84.6%, which indicates the potential of this platform for osteosarcoma treatment, particularly for advanced and relapsed cases. The proposed polysaccharide nanopartide would be a promising drug delivery platform to advance osteosarcoma nanomedicine.
基金Acknowledgments We gratefully acknowledge the financial support from the National Natural Science Foundation of China （No.50733003 and No.50973109）, the Major Project of International Cooperation from the Ministry of Science and Technology of China （2010DFB50890） and the Interdiscipline Subject Project from Jilin University （2011J018）.
文摘Mesoporous nano-hydroxyapatite （n-HA） has gained more and more attention as drug storage and release hosts. The aim of this study is to observe the effect of the ratio of surfactant to the theoretical yield of HA on the mesoporous n-HA, then to reveal the effect of the mesoporous nanostructure on protein delivery. The mesoporous n-HA was synthesized using the wet precipitation in the presence of cetyltrimethylammonium bromide （CTAB） at ambient temperature and normal atmospheric pressure. The morphology, size, crystalline phase, chemical composition and textural characteristics of the product were well characterized by X-ray Powder Diffraction （XRD）, Fourier Transform Infrared Spectroscopy （FTIR）, Scanning Electron Microscopy （SEM）, Transmission Electron Microscopy （TEM）, Dynamic Light Scattering （DLS） and N2 adsorption/desorption, respectively. The protein adsorption/release studies were also carried out by using Bovine Serum Albumin （BSA） as a model protein. The results reveal that the mesoporous n-HA synthesized with CTAB exhibits high pure phase, low crystallinity and the typical characteristics of the mesostructure. The BSA loading increases with the specific surface area and the pore volume of n-HA, and the release rates of BSA are different due to their different pore sizes and pore structures, n-HA synthesized with 0.5% CTAB has the highest BSA loading and the slowest release rate because of its highest surface area and smaller pore size. These mesoporous n-HA materials demonstrate a potential application in the field of protein delivery due to their bioactive, biocompatible and mesoporous properties.
基金This research was financially supported by Na- tional Natural Science Foundation of China （Projects 51103149, 51273195 and 51321062）.
文摘In order to architecturally and functionally mimic native Extracellular Matrix （ECM）, a novel micro/nano-fibrous scaffold of hydroxyapetite/poly（lactide-co-glycolide） （HA/PLGA） composite was successfully prepared by melt-spinning method. A porous three-dimensional scaffold fabricated by melt-molding particulate-leaching method was used as control. This kind of scaffold comprising both nanofiber and microfiber had an original structure including a nano-network favorable for cell adhe- sion, and a micro-fiber providing a strong skeleton for support. The microfibers and nanofibers were blended homogeneously in scaffold and the compression strength reached to 6.27 MPa, which was close to human trabecular bone. The typical mi- cro/nano-fibrous structure was more benefcial for the proliferation and differentiation of Bone Mesenehymal Stem Cells （BMSCs）. The calcium deposition and Alkaline Phosphatase （ALP） activity were evaluated by the differentiation of BMSCs, and the results indicated that the temporary ECM was very beneficial for the differentiation of BMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, micro/nano-fibrous scaffold was used for the purpose of rapid bone remodeling in the defect area. The results showed that a distinct bony callus of bridging was observed at 12 weeks post-surgery and the expression of osteogenesis-related genes （bone-morphogenetic protein-2, Osteonectin, collagen-I） increased because of the ECM-like structure. Based on the results, the novel micro/nano-fibrous scaffold might be a promising candidate for bone tissue engi- neering.
基金The study was financially supported by the National Natural Science Foundation of China(Grant Nos.51973216,51873207,51833010,and 51803006)the Science and Technology Development Program of Jilin Province(Grant No.20200404182YY)the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2019005).
文摘Intravesical chemotherapy has been recommended after the gold standard of transurethral resection of the bladder tumor to prevent bladder cancer(BC)from local recurrence in the clinic.However,due to rapid urine excretion and barrier protection of the bladder wall,the clinical performances of chemotherapeutic drugs are severely compromised.In the present work,a smart positively charged disulfide-crosslinked nanogel of oligoarginine-poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine)(R_(9)-PEG-P(LP-co-LC))was prepared to prolong the retention period and enhance the penetration capability of chemotherapeutic agent toward the bladder wall.PEG significantly improved the aqueous dispersibility of the 10-hydroxycamptothecin(HCPT)-loaded R_(9)-PEG-P(LP-co-LC)(i.e.,R_(9)NG/HCPT)and enhanced the mucoadhesive capability by the nonspecific interaction between PEG chain and the bladder mucosa accompanied with the electrostatic interaction between the cationic R_(9)and negatively charged bladder mucosa.Besides,R_(9),as a cell-penetrating peptide,efficiently penetrated through the cell membrane and delivered carried cargo.The disulfide bond endowed the selective release behavior of HCPT triggered by the intracellular reductive microenvironment.As an advanced chemotherapeutic nanoformulation,the smart R_(9)NG/HCPT demonstrated superior cytotoxicity against human BC 5637 cells in vitro and remarkably enhanced tumor suppression activity toward orthotopic BC models of mouse and rat in vivo,indicating its great potential in the clinical intravesical BC chemotherapy.
基金This work was supported by the National Natural Science Foundation of China(51925305,51873208,51973217,51520105004 and 51803210)National Science and Technology Major Projects for Major New Drugs Innovation and Development(2018ZX09711003-012)and Jilin Province Science and Technology Development Program(20180414027GH and 20200201075JC).
文摘Tumor nanovaccines have potential applications in the prevention and treatment of malignant tumors.However,it remains a longstanding challenge in exploiting efficient nanocarriers for inducing potent specifically cellular immune responses.Toward this objective,we herein explore an intensive tumor immunotherapeutic strategy by combining mannosylated nanovaccines and gene regulated PD-L1 blockade for immune stimulation and killing activity.Here,we fabricate a mannose modified PLL-RT(Man-PLL-RT)mediated nanovaccines with dendritic cells(DCs)targeting capacity.Man-PLL-RT is capable of co-encapsulating with antigen(ovalbumin,OVA)and adjuvant(unmethylated cytosine-phosphate-guanine,CpG)by electrostatic interaction.This positively charged Man-PLL-RT/OVA/CpG nanovaccines can facilitate the endocytosis,maturation and cross presentation in DCs.However,the nanovaccines arouse limited inhibition of tumor growth,which is mainly due to the immunosuppressed microenvironment of tumors.Combining tumor nanovaccines with gene regulated PD-L1 blockade leads to an obvious tumor remission in B16F10 melanoma bearing mice.The collaborative strategy provides essential insights to boost the benefits of tumor vaccines by regulating the checkpoint blockade with gene therapy.
基金The authors are thankful to the National Natural Science Foundation of China(Nos.51925305,51803210,51520105004,51873208,51973217 and 51833010)Jilin province science and technology development program(Nos.20200201075JC,20180414027GH)National Science and Technology Major Projects for Major New Drugs Innovation and Development(No.2018ZX09711003-012).
文摘Despite of the promising achievements of immune checkpoints blockade therapy(ICB) in the clinic,which was often limited by low objective responses and severe side effects.Herein,we explored a synergistic strategy to combine in situ vaccination and gene-mediated anti-PD therapy,which was generated by unmethylated cytosine-phosphate-guanine(CpG) and pshPD-L1 gene co-delivery.PEI worked as the delivery carrier to co-deliver the CpG and pshPD-L1 genes,the formed PDC(PEI/DNA/CpG)nanoparticles were further shielded by aldehyde modified polyethylene glycol(OHC-PEG-CHO) via pH responsive Schiff base reaction for OHC-PEG-CHO-PEI/DNA/CpG nanoparticles(P(PDC) NPs) prepa ration.All steps could be finished within 30 min.Such simple nanoparticles achieved the synergistic antitumor efficacy in B16 F10 tumor-bearing mice,and the amplified T cell responses,together with enhanced NK cells infiltration were observed after the combined treatments.In addition,the pH responsive delivery system reduced the side effects triggered by anti-PD therapy.The facile and effective combination strategy we presented here might provide a novel treatment for tumor inhibition.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.51303174,51273196,51203153,51233004,51390484,and 51321062)the Scientific Development Program of Jilin Province(Nos.20140520050JH and 20140309005GX)the Science and Technology Planning Project of Changchun City(No.14KG045).
文摘The osteochondral defects caused by vigorous trauma or physical disease are difficult to be managed.Tissue engineering provides a possible option to regenerate the damaged osteochondral tissues.For osteochondral reconstruction,one intact scaffold should be considered to support the regeneration of both cartilage and subchondral bone.Therefore,the biphasic scaffolds with the mimic structures of osteochondral tissues have been developed to close this chasm.A variety of biomimetic bilayer scaffolds fabricated from natural or synthetic polymers,or the ones loading with growth factors,cells,or both of them make great progresses in osteochondral defect repair.In this review,the preparation and in vitro and/or in vivo verification of bioinspired biphasic scaffolds are summarized and discussed,as well as the prospect is predicted.
基金the financial support from the National Natural Science Foundation of China(Nos.51973216,51873207,51803006,51833010,51673190 and 51520105004)the Science and Technology Development Program of Jilin Province(No.20190201068JC)+2 种基金the National Key Research and Development Program of China(No.2016YFC1100701)the Youth Talents Promotion Project of Jilin Province(No.181909)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019005)。
文摘Polypeptides are one kind of promising biodegradable and biocompatible biomedical polymers with the structural units of various a-amino acids.Polypeptides were first polymerized by the ring-opening polymerization(ROP)of α-amino acid N-carboxyanhydrides(NCAs)by Leuchs and Hermann in 1906.In the past decades,several effective strategies,including the selection of initiators,the adjustment of reaction conditions,and the introduction of catalysts,have been reported to improve the controllability of the ROP of various a-amino acid NCAs to synthesize different polypeptides with precise chemical structures and low polydispersity indexes.In this Review,the strategies,mechanisms,challenges,and opportunities for controlled synthesis of polypeptides by the ROP of differentα-amino acid NCAs have been declared.
