Dihydroartemisinin(DHA),a first-line antimalarial drug,has demonstrated great anticancer effects in many types of tumors,including liver cancer,glioblastoma,and pancreatic cancer.Due to its abilities to induce program...Dihydroartemisinin(DHA),a first-line antimalarial drug,has demonstrated great anticancer effects in many types of tumors,including liver cancer,glioblastoma,and pancreatic cancer.Due to its abilities to induce programmed cell death(PCD;apoptosis,autophagy and ferroptosis),inhibit tumor metastasis and angiogenesis,and modulate the tumor microenvironment,DHA could become an antineoplastic agent in the foreseeable future.However,the therapeutic efficacy of DHA is compromised owing to its inherent disadvantages,including poor stability,low aqueous solubility,and short plasma halflife.To overcome these drawbacks,nanoscale drug delivery systems(NDDSs),such as polymeric nanoparticles(NPs),liposomes,and metal-organic frameworks(MOFs),have been introduced to maximize the therapeutic efficacy of DHA in either single-drug or multidrug therapy.Based on the beneficial properties of NDDSs,including enhanced stability and solubility of the drug,prolonged circulation time and selective accumulation in tumors,the outcomes of DHA-loaded NDDSs for cancer therapy are significantly improved compared to those of free DHA.This reviewfirst summarizes the current understanding of the anticancer mechanisms of DHA and then provides an overview of DHA-including nanomedicines,aiming to provide inspiration for further application of DHA as an anticancer drug.展开更多
Drug delivery systems able to deliver the required dose of the drug to the target level use active or passive nano metric designed systems. In the earlier researches, carbon nanocones are used for transferring the ser...Drug delivery systems able to deliver the required dose of the drug to the target level use active or passive nano metric designed systems. In the earlier researches, carbon nanocones are used for transferring the serum to damaged proteins and damaged cancer cellules. In this lecture, stability analysis of drug delivery to damaged cancer cellutes is studied in the shape of single-walled carbon nanocone. In this method, each atom is considered as node and interactions between them are supposed as 3D-beam elements. By supposing that potential energy in macro relations is equal to the nano relations, nano-drug characteristics can be calculated. Then shape functions can be extracted to use in blood＇s FEM model and using reduced-order method, divergence velocities of carbon nanocone can be found. In this lecture, carbon nanocones are modeled with different dimensions and boundary conditions and stability of them in blood flow is studied and optimized carbon nanocone is selected in blood flow. Results show that conical nano-drug structures have more efficiency in blood flow rather than tube nano-drug structures and by increasing length of carbon nanocones, dimensionless stability parameter decreased and by increasing declination angle of carbon nanocones, dimensionless stability parameter increased.展开更多
The considerable development of carrier-free nanodrugs has been achieved due to their high drug-loading capability,simple preparation method,and offering“all-in-one”functional platform features.However,the native de...The considerable development of carrier-free nanodrugs has been achieved due to their high drug-loading capability,simple preparation method,and offering“all-in-one”functional platform features.However,the native defects of carrier-free nanodrugs limit their delivery and release behavior throughout the in vivo journey,which significantly compromise the therapeutic efficacy and hinder their further development in cancer treatment.In this review,we summarized and discussed the recent strategies to enhance drug delivery and release of carrier-free nanodrugs for improved cancer therapy,including optimizing the intrinsic physicochemical properties and external modification.Finally,the corresponding challenges that carrier-free nanodrugs faced are discussed and the future perspectives for its application are presented.We hope this review will provide constructive information for the rational design of more effective carrier-free nanodrugs to advance therapeutic treatment.展开更多
Objective:To construct methotrexate(MTX)-chitosan(CS)-chuanxiongmuizine(TMP)nano-delivery system MTX-CS-TMP-NPs,and to investigate its effect on the telomerase activity of cervical cancer Hela cells.Methods:MTX-CS and...Objective:To construct methotrexate(MTX)-chitosan(CS)-chuanxiongmuizine(TMP)nano-delivery system MTX-CS-TMP-NPs,and to investigate its effect on the telomerase activity of cervical cancer Hela cells.Methods:MTX-CS and MTX-CS-TMP-NPs were prepared by amide reaction and ionic gel method,and the encapsulation rate and drug loading rate were observed.MTT method and TRAP method were used to detect Hela cells and telomerase activity,and to compare the difference of telomerase activity of MTX,MTX-CS,and MTX-CS-TMP-NPs on cervical cancer Hela cells.Results:In this study,the total amount of TMP was 150μg,of which the amount of free TMP was(26.46±1.72)μg,the encapsulation rate of TMP was(82.36±0.01)%,and the drug loading was(17.62±0.23)mg.The activity of Hela cells increased with the extension of time,and the OD value of Hela cell activity(1.24±0.05)was lower than that of the other three groups at 72 h of treatment,and the difference was statistically significant(P<0.05).The telomerase activity of He La cells in the MTX-CS-TMP-NPs solution treatment group was(0.23±0.12)%lower than that of the other three groups,with statistically significant difference(P<0.05).Conclusion:MTX-CS-TMP-NPs may effectively reduce the activity and telomerase activity of cervical cancer Hela cells,showing its potential anti-cervical cancer effect.展开更多
As one of the most important components of caveolae,caveolin-1 is involved in caveolaemediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and me...As one of the most important components of caveolae,caveolin-1 is involved in caveolaemediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction.In recent years,the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored.In addition,the interplay between caveolin-1 and nano-drugs is bidirectional.Caveolin-1 could determine the intracellular biofate of specifc nano-drugs,preventing from lysosomal degradation,and facilitate them penetrate into deeper site of tumors by transcytosis;while some nanocarriers could also affect caveolin-1 levels in tumor cells,thereby changing certain biophysical function of cells.This article reviews the role of caveolin-1 in tumor prognosis,chemotherapeutic drug resistance,antibody drug sensitivity,and nano-drug delivery,providing a reference for the further application of caveolin-1 in nano-drug delivery systems.展开更多
Due to the special physiological and pathological characteristics of gliomas,most therapeutic drugs are prevented from entering the brain.To improve the poor prognosis of existing therapies,researchers have been conti...Due to the special physiological and pathological characteristics of gliomas,most therapeutic drugs are prevented from entering the brain.To improve the poor prognosis of existing therapies,researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy.Although these strategies can be used clinically to overcome the blood-brain barrier(BBB),the accurate delivery of drugs to the glioma lesions cannot be ensured.Nano-drug delivery systems(NDDS)have been widely used for precise drug delivery.In recent years,researchers have gathered their wisdom to overcome barriers,so many well-designed NDDS have performed prominently in preclinical studies.These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions,drug release in response to the glioma microenvironment,biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein,and carriers created according to the active ingredients of traditional Chinese medicines.We reviewed these well-designed NDDS in detail.Furthermore,we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy,and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.展开更多
In recent years,owing to the miniaturization of the fluidic environment,microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems(NDDSs)production processes.Compared with...In recent years,owing to the miniaturization of the fluidic environment,microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems(NDDSs)production processes.Compared with traditional methods,microfluidics improves the controllability and uniformity of NDDSs.The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs,including particle size,distribution and morphology,resulting in narrow particle size distribution and high drug-loading capacity.The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up.In this review,we provide a comprehensive summary of microfluidics-based NDDSs,including the fundamentals of microfluidics,microfluidic synthesis of NDDSs,and their industrialization.The challenges of microfluidicsbased NDDSs in the current status and the prospects for future development are also discussed.We believe that this review will provide good guidance for microfluidics-based NDDSs.展开更多
In recent decades,cancer stem cells(CSCs)have been increasingly identified in many malignancies.CSC-related signaling pathways and their functions provide new strategies for treating cancer.The aberrant activation of ...In recent decades,cancer stem cells(CSCs)have been increasingly identified in many malignancies.CSC-related signaling pathways and their functions provide new strategies for treating cancer.The aberrant activation of related signaling pathways(e.g.,Wnt,Notch,and Hedgehog pathways)has been linked to multiple types of malignant tumors,which makes these pathways attractive targets for cancer therapy.CSCs display many characteristic features,such as self-renewal,differentiation,high tumorigenicity,and drug resistance.Therefore,there is an urgent need to develop new therapeutic strategies to target these pathways to control stem cell replication,survival,and differentiation.Notable crosstalk occurs among different signaling pathways and potentially leads to compensatory escape.Therefore,multitarget inhibitors will be one of the main methods to overcome the drug resistance of CSCs.Many small molecule inhibitors of components of signaling pathways in CSCs have entered clinical trials,and some inhibitors,such as vismodegib,sonidegib,and glasdegib,have been approved.Tumor cells are susceptible to sonidegib and vismodegib resistance due to mutations in the Smo protein.The signal transducers and activators of transcription 3(STAT3)inhibitor BBI608 is being evaluated in a phase III trial for a variety of cancers.Structural derivatives of BBI608 are the main focus of STAT3 inhibitor development,which is another strategy for CSC therapy.In addition to the potential pharmacological inhibitors targeting CSCrelated signaling pathways,other methods of targeting CSCs are available,such as nano-drug delivery systems,mitochondrion targeting,autophagy,hyperthermia,immunotherapy,and CSC microenvironment targeting.In addition,we summarize the latest advances in the clinical development of agents targeting CSC-related signaling pathways and other methods of targeting CSCs.展开更多
This article discusses the various blood interactions that may occur with various types of nano drug-loading systems. Nanoparticles enter the blood circulation as foreign objects. On the one hand, they may cause a ser...This article discusses the various blood interactions that may occur with various types of nano drug-loading systems. Nanoparticles enter the blood circulation as foreign objects. On the one hand, they may cause a series of inflammatory reactions and immune reactions, resulting in the rapid elimination of immune cells and the reticuloendothelial system, affecting their durability in the blood circulation. On the other hand, the premise of the drug-carrying system to play a therapeutic role depends on whether they cause coagulation and platelet activation, the absence of hemolysis and the elimination of immune cells. For different forms of nano drug-carrying systems, we can find the characteristics, elements and coping strategies of adverse blood reactions that we can find in previous researches. These adverse reactions may include destruction of blood cells, abnormal coagulation system, abnormal effects of plasma proteins, abnormal blood cell behavior, adverse immune and inflammatory reactions, and excessive vascular stimulation. In order to provide help for future research and formulation work on the blood compatibility of nano drug carriers.展开更多
Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of ...Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.展开更多
Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism ...Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism spectrum disorder,and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes.The treatment of neurodegenerative and neurodevelopmental conditions,together affecting~120 million people worldwide,is challenged by the blood—brain barrier(BBB)and the blood—cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS.The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions.This pathway is more efficient for nanoparticles than for solutions,hence,the research on intranasal nano-drug delivery systems has grown exponentially over the last decade.Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility.This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions,the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them.Then,a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.展开更多
Nucleic acid therapeutics,which involve transferring exogenous genes inside target cells,are a promising clinical treatment option that can regulate gene expression at the transcriptional or post-transcriptional level...Nucleic acid therapeutics,which involve transferring exogenous genes inside target cells,are a promising clinical treatment option that can regulate gene expression at the transcriptional or post-transcriptional level.Ideally,this kind of treatment modality will not lead to an unwanted immune response.Compared with traditional treatment methods,nucleic acid therapeutics can achieve prolonged and stable curative effects.As an emerging treatment method,nucleic acid therapeutics have played an increasingly important role in clinical settings for the treatment of various conditions,including infectious diseases,cancer,immune-related diseases,and monogenetic diseases.To date,a large number of clinical trials have been conducted,and more than 30 nucleic acid drugs have been approved,highlighting the strong potential of this approach in clinical practice.Diverse carriers are used to protect nucleic acids from being degraded and to help them reach their targets accurately.However,some carriers are known to cause negative effects on the release and expression of nucleic acid drugs as well as adverse effects such as allergic reactions and accumulation in the liver.Therefore,biosafety assessment of delivery systems before their application in clinical settings is critical.In this review,we describe different delivery systems for nucleic acid drugs and discuss their biosafety in both preclinical and clinical studies,with particular focus on the carriers themselves,drug administration method,and overall treatment of the disease.展开更多
Macrophages have a leading position in the tumor microenvironment(TME)which paves the way to carcinogenesis.Initially,monocytes and macrophages are recruited to the sites where the tumor develops.Under the guidance of...Macrophages have a leading position in the tumor microenvironment(TME)which paves the way to carcinogenesis.Initially,monocytes and macrophages are recruited to the sites where the tumor develops.Under the guidance of different microenvironmental signals,macrophages would polarize into two functional phenotypes,named as classically activated macrophages(M1)and alternatively activated macrophages(M2).Contrary to the anti-tumor effect of M1,M2 exerts anti-inflammatory and tumorigenic characters.In progressive tumor,M2 tumor-associated macrophages(TAMs)are in the majority,being vital regulators reacting upon TME.This review elaborates on the role of TAMs in tumor progression.Furthermore,prospective macrophage-focused therapeutic strategies,including drugs not only in clinical trials but also at primary research stages,are summarized followed by a discussion about their clinical application values.Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.展开更多
A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer.However,its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenou...A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer.However,its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier.Herein,we report an albumin-bound tumor redoxresponsive paclitaxel prodrugs nano-delivery strategy.Using diverse linkages(thioether bond and disulfide bond),paclitaxel(PTX)was conjugated with an albumin-binding maleimide(MAL)functional group.These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles(NPs)in aqueous solution without any excipients.By immediately binding to blood circulating albumin after intravenous administration,NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo,facilitating PTX prodrugs accumulation in the tumor region via albumin receptormediated active targeting.The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells.Moreover,disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo.This simple and facile strategy integrates the biomimetic characteristic of albumin,tumor redox-responsive on-demand drug release,and provides new opportunities for the development of the high-efficiency antitumor nanomedicines.展开更多
基金supported by the National Natural Science Foundation of China[51922111]the Science and Technology Development Fund,Macao SAR[File no.0124/2019/A3]Guangdong-Hong Kong-Macao Joint Laboratory of Optoelectronic and Magnetic Functional Materials[2019B121205002].
文摘Dihydroartemisinin(DHA),a first-line antimalarial drug,has demonstrated great anticancer effects in many types of tumors,including liver cancer,glioblastoma,and pancreatic cancer.Due to its abilities to induce programmed cell death(PCD;apoptosis,autophagy and ferroptosis),inhibit tumor metastasis and angiogenesis,and modulate the tumor microenvironment,DHA could become an antineoplastic agent in the foreseeable future.However,the therapeutic efficacy of DHA is compromised owing to its inherent disadvantages,including poor stability,low aqueous solubility,and short plasma halflife.To overcome these drawbacks,nanoscale drug delivery systems(NDDSs),such as polymeric nanoparticles(NPs),liposomes,and metal-organic frameworks(MOFs),have been introduced to maximize the therapeutic efficacy of DHA in either single-drug or multidrug therapy.Based on the beneficial properties of NDDSs,including enhanced stability and solubility of the drug,prolonged circulation time and selective accumulation in tumors,the outcomes of DHA-loaded NDDSs for cancer therapy are significantly improved compared to those of free DHA.This reviewfirst summarizes the current understanding of the anticancer mechanisms of DHA and then provides an overview of DHA-including nanomedicines,aiming to provide inspiration for further application of DHA as an anticancer drug.
文摘Drug delivery systems able to deliver the required dose of the drug to the target level use active or passive nano metric designed systems. In the earlier researches, carbon nanocones are used for transferring the serum to damaged proteins and damaged cancer cellules. In this lecture, stability analysis of drug delivery to damaged cancer cellutes is studied in the shape of single-walled carbon nanocone. In this method, each atom is considered as node and interactions between them are supposed as 3D-beam elements. By supposing that potential energy in macro relations is equal to the nano relations, nano-drug characteristics can be calculated. Then shape functions can be extracted to use in blood＇s FEM model and using reduced-order method, divergence velocities of carbon nanocone can be found. In this lecture, carbon nanocones are modeled with different dimensions and boundary conditions and stability of them in blood flow is studied and optimized carbon nanocone is selected in blood flow. Results show that conical nano-drug structures have more efficiency in blood flow rather than tube nano-drug structures and by increasing length of carbon nanocones, dimensionless stability parameter decreased and by increasing declination angle of carbon nanocones, dimensionless stability parameter increased.
基金supported by grants from the National Key Research and Development Program of China(No.2018YFC1106103)the National Natural Science Foundation of China(Grant No.51973135).
文摘The considerable development of carrier-free nanodrugs has been achieved due to their high drug-loading capability,simple preparation method,and offering“all-in-one”functional platform features.However,the native defects of carrier-free nanodrugs limit their delivery and release behavior throughout the in vivo journey,which significantly compromise the therapeutic efficacy and hinder their further development in cancer treatment.In this review,we summarized and discussed the recent strategies to enhance drug delivery and release of carrier-free nanodrugs for improved cancer therapy,including optimizing the intrinsic physicochemical properties and external modification.Finally,the corresponding challenges that carrier-free nanodrugs faced are discussed and the future perspectives for its application are presented.We hope this review will provide constructive information for the rational design of more effective carrier-free nanodrugs to advance therapeutic treatment.
文摘Objective:To construct methotrexate(MTX)-chitosan(CS)-chuanxiongmuizine(TMP)nano-delivery system MTX-CS-TMP-NPs,and to investigate its effect on the telomerase activity of cervical cancer Hela cells.Methods:MTX-CS and MTX-CS-TMP-NPs were prepared by amide reaction and ionic gel method,and the encapsulation rate and drug loading rate were observed.MTT method and TRAP method were used to detect Hela cells and telomerase activity,and to compare the difference of telomerase activity of MTX,MTX-CS,and MTX-CS-TMP-NPs on cervical cancer Hela cells.Results:In this study,the total amount of TMP was 150μg,of which the amount of free TMP was(26.46±1.72)μg,the encapsulation rate of TMP was(82.36±0.01)%,and the drug loading was(17.62±0.23)mg.The activity of Hela cells increased with the extension of time,and the OD value of Hela cell activity(1.24±0.05)was lower than that of the other three groups at 72 h of treatment,and the difference was statistically significant(P<0.05).The telomerase activity of He La cells in the MTX-CS-TMP-NPs solution treatment group was(0.23±0.12)%lower than that of the other three groups,with statistically significant difference(P<0.05).Conclusion:MTX-CS-TMP-NPs may effectively reduce the activity and telomerase activity of cervical cancer Hela cells,showing its potential anti-cervical cancer effect.
文摘As one of the most important components of caveolae,caveolin-1 is involved in caveolaemediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction.In recent years,the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored.In addition,the interplay between caveolin-1 and nano-drugs is bidirectional.Caveolin-1 could determine the intracellular biofate of specifc nano-drugs,preventing from lysosomal degradation,and facilitate them penetrate into deeper site of tumors by transcytosis;while some nanocarriers could also affect caveolin-1 levels in tumor cells,thereby changing certain biophysical function of cells.This article reviews the role of caveolin-1 in tumor prognosis,chemotherapeutic drug resistance,antibody drug sensitivity,and nano-drug delivery,providing a reference for the further application of caveolin-1 in nano-drug delivery systems.
基金financial support from National Natural Science Foundation of China(Nos.81903557 and 82074024)Natural Science Foundation of Jiangsu Province(No.BK20190802,China)+3 种基金Natural Science Foundation Youth Project of Nanjing University of Chinese Medicine(No.NZY81903557,China)the Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine(No.2020YLXK019,China)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.19KJB350003,China)College Students’Innovative Entrepreneurial Training Plan Program of Nanjing University of Chinese Medicine(No.202010315XJ040,China)。
文摘Due to the special physiological and pathological characteristics of gliomas,most therapeutic drugs are prevented from entering the brain.To improve the poor prognosis of existing therapies,researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy.Although these strategies can be used clinically to overcome the blood-brain barrier(BBB),the accurate delivery of drugs to the glioma lesions cannot be ensured.Nano-drug delivery systems(NDDS)have been widely used for precise drug delivery.In recent years,researchers have gathered their wisdom to overcome barriers,so many well-designed NDDS have performed prominently in preclinical studies.These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions,drug release in response to the glioma microenvironment,biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein,and carriers created according to the active ingredients of traditional Chinese medicines.We reviewed these well-designed NDDS in detail.Furthermore,we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy,and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.
基金supported by the projects of National Natural Science Foundation of China(No.82073784,China)Jilin Province Science and Technology Development Program(No.20200801012GH,China)Industrial Technology Research and Development Projects from the Development and Reform Commission of Jilin Province Major Science and Technology Special Projects(20200504005YY,China)。
文摘In recent years,owing to the miniaturization of the fluidic environment,microfluidic technology offers unique opportunities for the implementation of nano drug delivery systems(NDDSs)production processes.Compared with traditional methods,microfluidics improves the controllability and uniformity of NDDSs.The fast mixing and laminar flow properties achieved in the microchannels can tune the physicochemical properties of NDDSs,including particle size,distribution and morphology,resulting in narrow particle size distribution and high drug-loading capacity.The success of lipid nanoparticles encapsulated mRNA vaccines against coronavirus disease 2019 by microfluidics also confirmed its feasibility for scaling up the preparation of NDDSs via parallelization or numbering-up.In this review,we provide a comprehensive summary of microfluidics-based NDDSs,including the fundamentals of microfluidics,microfluidic synthesis of NDDSs,and their industrialization.The challenges of microfluidicsbased NDDSs in the current status and the prospects for future development are also discussed.We believe that this review will provide good guidance for microfluidics-based NDDSs.
基金Supported by Natural Science Foundation of Liaoning Province,No.201602707
文摘In recent decades,cancer stem cells(CSCs)have been increasingly identified in many malignancies.CSC-related signaling pathways and their functions provide new strategies for treating cancer.The aberrant activation of related signaling pathways(e.g.,Wnt,Notch,and Hedgehog pathways)has been linked to multiple types of malignant tumors,which makes these pathways attractive targets for cancer therapy.CSCs display many characteristic features,such as self-renewal,differentiation,high tumorigenicity,and drug resistance.Therefore,there is an urgent need to develop new therapeutic strategies to target these pathways to control stem cell replication,survival,and differentiation.Notable crosstalk occurs among different signaling pathways and potentially leads to compensatory escape.Therefore,multitarget inhibitors will be one of the main methods to overcome the drug resistance of CSCs.Many small molecule inhibitors of components of signaling pathways in CSCs have entered clinical trials,and some inhibitors,such as vismodegib,sonidegib,and glasdegib,have been approved.Tumor cells are susceptible to sonidegib and vismodegib resistance due to mutations in the Smo protein.The signal transducers and activators of transcription 3(STAT3)inhibitor BBI608 is being evaluated in a phase III trial for a variety of cancers.Structural derivatives of BBI608 are the main focus of STAT3 inhibitor development,which is another strategy for CSC therapy.In addition to the potential pharmacological inhibitors targeting CSCrelated signaling pathways,other methods of targeting CSCs are available,such as nano-drug delivery systems,mitochondrion targeting,autophagy,hyperthermia,immunotherapy,and CSC microenvironment targeting.In addition,we summarize the latest advances in the clinical development of agents targeting CSC-related signaling pathways and other methods of targeting CSCs.
文摘This article discusses the various blood interactions that may occur with various types of nano drug-loading systems. Nanoparticles enter the blood circulation as foreign objects. On the one hand, they may cause a series of inflammatory reactions and immune reactions, resulting in the rapid elimination of immune cells and the reticuloendothelial system, affecting their durability in the blood circulation. On the other hand, the premise of the drug-carrying system to play a therapeutic role depends on whether they cause coagulation and platelet activation, the absence of hemolysis and the elimination of immune cells. For different forms of nano drug-carrying systems, we can find the characteristics, elements and coping strategies of adverse blood reactions that we can find in previous researches. These adverse reactions may include destruction of blood cells, abnormal coagulation system, abnormal effects of plasma proteins, abnormal blood cell behavior, adverse immune and inflammatory reactions, and excessive vascular stimulation. In order to provide help for future research and formulation work on the blood compatibility of nano drug carriers.
基金supported by the projects of National Natural Science Foundation of China(No.81973259,82073789,81803472)the project for Innovative Research Group at Higher Educational Institutions in Chongqing(CXQT20006,China).
文摘Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.
基金the NEVET Nanotechnology Grant of the Russell Berrie Nanotechnology Institute(RBNI)at Technion—Israel Institute of Technology(Israel)the Tamara and Harry Handelsman Academic Chair(Israel)for financial support。
文摘Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system(CNS)and result in their damage and death.Neurodevelopmental disorders include intellectual disability,autism spectrum disorder,and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes.The treatment of neurodegenerative and neurodevelopmental conditions,together affecting~120 million people worldwide,is challenged by the blood—brain barrier(BBB)and the blood—cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS.The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions.This pathway is more efficient for nanoparticles than for solutions,hence,the research on intranasal nano-drug delivery systems has grown exponentially over the last decade.Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility.This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions,the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them.Then,a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.
基金support from the National Natural Science Foundation of China(Nos.22161132008 and 81822024)the Natural Science Foundation of Shanghai,China(Nos.19520714100 and 19ZR1475800)the Project of Shanghai Jiao Tong University(2019QYA03 and YG2017ZD07).
文摘Nucleic acid therapeutics,which involve transferring exogenous genes inside target cells,are a promising clinical treatment option that can regulate gene expression at the transcriptional or post-transcriptional level.Ideally,this kind of treatment modality will not lead to an unwanted immune response.Compared with traditional treatment methods,nucleic acid therapeutics can achieve prolonged and stable curative effects.As an emerging treatment method,nucleic acid therapeutics have played an increasingly important role in clinical settings for the treatment of various conditions,including infectious diseases,cancer,immune-related diseases,and monogenetic diseases.To date,a large number of clinical trials have been conducted,and more than 30 nucleic acid drugs have been approved,highlighting the strong potential of this approach in clinical practice.Diverse carriers are used to protect nucleic acids from being degraded and to help them reach their targets accurately.However,some carriers are known to cause negative effects on the release and expression of nucleic acid drugs as well as adverse effects such as allergic reactions and accumulation in the liver.Therefore,biosafety assessment of delivery systems before their application in clinical settings is critical.In this review,we describe different delivery systems for nucleic acid drugs and discuss their biosafety in both preclinical and clinical studies,with particular focus on the carriers themselves,drug administration method,and overall treatment of the disease.
基金supported by the National Natural Science Foundation of China(Nos.81673022,81572952 and 81373346)National Key R&D Program of China(No.2017YFE0102200)
文摘Macrophages have a leading position in the tumor microenvironment(TME)which paves the way to carcinogenesis.Initially,monocytes and macrophages are recruited to the sites where the tumor develops.Under the guidance of different microenvironmental signals,macrophages would polarize into two functional phenotypes,named as classically activated macrophages(M1)and alternatively activated macrophages(M2).Contrary to the anti-tumor effect of M1,M2 exerts anti-inflammatory and tumorigenic characters.In progressive tumor,M2 tumor-associated macrophages(TAMs)are in the majority,being vital regulators reacting upon TME.This review elaborates on the role of TAMs in tumor progression.Furthermore,prospective macrophage-focused therapeutic strategies,including drugs not only in clinical trials but also at primary research stages,are summarized followed by a discussion about their clinical application values.Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.
基金supported by National Natural Science Foundation of China(No.81773656 and U1608283)Liaoning Revitalization Talents Program(No XLYC1808017,China)+2 种基金Key projects of Technology bureau in Shenyang(No.18400408,China)Key projects of Liaoning Province Department of Education(No.2017LZD03,China)111 Project(D20029,China)
文摘A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer.However,its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier.Herein,we report an albumin-bound tumor redoxresponsive paclitaxel prodrugs nano-delivery strategy.Using diverse linkages(thioether bond and disulfide bond),paclitaxel(PTX)was conjugated with an albumin-binding maleimide(MAL)functional group.These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles(NPs)in aqueous solution without any excipients.By immediately binding to blood circulating albumin after intravenous administration,NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo,facilitating PTX prodrugs accumulation in the tumor region via albumin receptormediated active targeting.The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells.Moreover,disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo.This simple and facile strategy integrates the biomimetic characteristic of albumin,tumor redox-responsive on-demand drug release,and provides new opportunities for the development of the high-efficiency antitumor nanomedicines.
