Nanoscale metal-organic frameworks(nano MOFs)have emerged as a promising biomedical nanoplatform because of their unique properties.However,the exploration of nano MOFs in photoacoustic(PA)imaging is still limited.Her...Nanoscale metal-organic frameworks(nano MOFs)have emerged as a promising biomedical nanoplatform because of their unique properties.However,the exploration of nano MOFs in photoacoustic(PA)imaging is still limited.Here,a novel hydrogen sulfide(H2 S)-activated nano copper-based MOF(Cu-MOF)was developed as a near-infrared(NIR)ratiometric PA probe for in vivo monitoring of endogenous H2 S level and orthotopic colorectal cancer imaging via in situ reaction of nano Cu-MOFs with endogenous H2 S that is closely associated with tumor growth and proliferation in colon cancer.The synthesized nano Cu-MOFs displayed excellent PA responsiveness towards tumor H2 S level with high selectivity and rapid kinetics.The result suggests the developed probe may provide a unique opportunity to investigate the malignant behaviors of H2 S-associated events in vivo.展开更多
Magnetic nanopartides have been used as drug delivery vehicles against a number of cancer cells. Most of these theranostic formulations have used solid iron oxide nanoparticles （SIONPs） loaded with chemotherapeutics...Magnetic nanopartides have been used as drug delivery vehicles against a number of cancer cells. Most of these theranostic formulations have used solid iron oxide nanoparticles （SIONPs） loaded with chemotherapeutics as nano-carrier formulation for both magnetic resonance imaging （MRI） and cancer therapy. In this study, we applied the dopamine-plus-human serum albumin （HSA） method to modify hollow iron oxide nanoparticles （HIONPs） and encapsuated doxorubicin （DOX） within the hollow porous structure of the nano-carrier. The new delivery system can load more drug than solid iron oxide nanoparticles of the same core size using the same coating strategy. The HIONPs-DOX formulation also has a pH-dependent drug release behaviour. Compared with free DOX, the HIONPs-DOX were more effectively uptaken by the multidrug resistant OVCAR8- ADR cells and consequently more potent in killing drug resistant cancer cells. MRI phantom and cell studies also showed that the HIONPs-DOX can decrease the T2 MRI signal intensity and can be used as a MR/contrast agent while acting as a drug delivery vehicle. For the first time, the dual application of chemo drug transport and MR imaging using the HIONPs-DOX formulation was achieved against both DOX-sensitive and DOX-resistant cancer cells.展开更多
Inorganic nanoparticles have been introduced into biological systems as useful probes for in vitro diagnosis and in vivo imaging, due to their relatively small size and exceptional physical and chemical properties. A ...Inorganic nanoparticles have been introduced into biological systems as useful probes for in vitro diagnosis and in vivo imaging, due to their relatively small size and exceptional physical and chemical properties. A new kind of color- tunable Gd-Zn-Cu-In-S/ZnS （GZCIS/ZnS） quantum dots （QDs） with stable crystal structure has been successfully synthesized and utilized for magnetic resonance （MR） and fluorescence dual modality imaging. This strategy allows successful fabrication of GZCIS/ZnS QDs by incorporating Gd into ZCIS/ZnS QDs to achieve great MR enhancement without compromising the fluorescence properties of the initial ZCIS/ZnS QDs. The as-prepared GZCIS/ZnS QDs show high T1 MR contrast as well as ＂color-tunable＂ photoluminescence （PL） in the range of 550-725 nm by adjusting the Zn/Cu feeding ratio with high PL quantum yield （QY）. The GZCIS/ZnS QDs were transferred into water via a bovine serum albumin （BSA） coating strategy. The resulting Cd-free GZCIS/ZnS QDs reveal negligible cytotoxicity on both HeLa and A549 cells. Both fluorescence and MR imaging studies were successfully performed in vitro and in vivo. The results demonstrated that GZCIS/ZnS QDs could be a dual-modal contrast agent to simultaneously produce strong MR contrast enhancement as well as fluorescence emission for in vivo imaging.展开更多
A symmetric pillararene-based receptor containing ten triazole units was synthesized.Interestingly,it formed 1:1 complexes instead of 1:2 with different halide anions.This was caused by the cooperative multivalent hyd...A symmetric pillararene-based receptor containing ten triazole units was synthesized.Interestingly,it formed 1:1 complexes instead of 1:2 with different halide anions.This was caused by the cooperative multivalent hydrogen-bond interactions between the triazole protons on one side of the receptor and the halide anion,which changed its structure from pillar to conical.However,by the regulation of the effector F-,it can work like an excavator grapple selectively grasps a PF6-anion.展开更多
Cancer chemotherapy has been limited by its side effects and multidrug resistance （MDR）, the latter of which is partially caused by drug efflux from cancer cells. Thus, targeted drug delivery systems that can circum...Cancer chemotherapy has been limited by its side effects and multidrug resistance （MDR）, the latter of which is partially caused by drug efflux from cancer cells. Thus, targeted drug delivery systems that can circumvent MDR are needed. Here, we report multifunctional DNA nanoflowers （NFs） for targeted drug delivery to both chemosensitive and MDR cancer cells that circumvented MDR in both leukemia and breast cancer cell models. NFs are self-assembled via potential co-precipitation of DNA and magnesium pyrophosphate generated by rolling circle replication, during which NFs are incorporated using aptamers for specific cancer cell recognition, fluorophores for bioimaging, and doxorubicin （Dox）- binding DNA for drug delivery. NF sizes are tunable （down to N200 nm in diameter）, and the densely packed drug-binding motifs and porous intrastructures endow NFs with a high drug-loading capacity （71.4%, wt/wt）. Although the Dox- loaded NFs （NF-Dox） are stable at physiological pH, drug release is facilitated under acidic or basic conditions. NFs deliver Dox into target chemosensitive and MDR cancer cells, preventing drug efflux and enhancing drug retention in MDR cells. NF-Dox induces potent cytotoxicity in both target chemosensitive cells and MDR cells, but not in nontarget cells, thus concurrently circumventing MDR and reducing side effects. Overall, these NFs are promising tools for circumventing MDR in targeted cancer therapy.展开更多
Endo/lysosomal escape and gene release are two critical bottlenecks in gene delivery.Herein,a novel photo-controllable metal-organic frameworks(MOFs)nanoswitch is rationally designed for enhancing small interfering RN...Endo/lysosomal escape and gene release are two critical bottlenecks in gene delivery.Herein,a novel photo-controllable metal-organic frameworks(MOFs)nanoswitch is rationally designed for enhancing small interfering RNA(siRNA)delivery.One single laser triggers the“off-to-on”switching of MOFs nanocomplexes,inducing significant siRNA release accompanied by rapid MOFs dissociation into protonatable 2-methylimidazalo and osmotic rupturing Zn2+ions,which cooperatively contribute to remarkable endo/lysosomal rupture(∼90%).The simultaneous endo/lysosomal rupture and release enable a high spatio-temporal control on RNA interference for effective cancer therapy.Notably,the“off-to-on”switching also activates fluorescence recovery for real-time monitoring siRNA delivery.The nanoswitch could easily be extended to deliver other therapeutic agents(e.g.,DNA,protein,anticancer drug)for overcoming endo/lysosomal entrapment.展开更多
The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycop...The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycoprotein(P-gp) in tumor cells. Here, we report a novel chemosensitizing agent, XMD8-92,which can down-regulate P-gp. To enhance the specificity of MDR chemotherapy, a promising nanotheranostic micelle system based on poly(ethylene glycol)-blocked-poly(L-leucine)(PEG-b-Leu) was developed to simultaneously carry the anticancer drug doxorubicin, chemosensitizing agent XMD8-92, and superparamagnetic iron oxide nanoparticles(SPIOs). Featured with MDR environmentally responsive dual-targeting capability, controllable drug delivery, and efficient magnetic resonance(MR) imaging characteristics, the prepared nanotheranostics(DXS@NPs) showed outstanding in vitro cytotoxicity on MDR cells(SCG 7901/VCR) with only 53% of cells surviving compared to 90% of DOX-treated cells.Furthermore, efficient tumor inhibition and highly reduced systemic toxicity were exhibited by MDR tumor-bearing mice treated with DXS@NPs. Overall, the environmentally responsive dual-targeting nanotheranostics represent a promising approach for overcoming cancer MDR.展开更多
基金the National Nature Sciences Foundation of China(2163500221874024)+2 种基金the joint research projects of Health and Education Commission of Fujian Province(2019-WJ-20)the Intramural Research Program,National Institute of Biomedical Imaging and BioengineeringNational Institutes of Health。
文摘Nanoscale metal-organic frameworks(nano MOFs)have emerged as a promising biomedical nanoplatform because of their unique properties.However,the exploration of nano MOFs in photoacoustic(PA)imaging is still limited.Here,a novel hydrogen sulfide(H2 S)-activated nano copper-based MOF(Cu-MOF)was developed as a near-infrared(NIR)ratiometric PA probe for in vivo monitoring of endogenous H2 S level and orthotopic colorectal cancer imaging via in situ reaction of nano Cu-MOFs with endogenous H2 S that is closely associated with tumor growth and proliferation in colon cancer.The synthesized nano Cu-MOFs displayed excellent PA responsiveness towards tumor H2 S level with high selectivity and rapid kinetics.The result suggests the developed probe may provide a unique opportunity to investigate the malignant behaviors of H2 S-associated events in vivo.
基金Acknowledgements This research was supported in part by the National Basic Research Program of China （973 Program, Nos. 2013CB733802 and 2010CB934602） the National Science Foundation of China （NSFC, Nos. 81101101, 81201086, 81201129, 81201190, 51273165, 51172005 and 81028009）+1 种基金 the Chinese Academy of Sciences Professorship for Senior International Scientists （No. 2011T2J06） and the Intramural Research Program （IRP） of the National Institute of Biomedical Imaging and Bioengineering （NIBIB）, National Institutes of Health （NIH）. R. X. is partially supported by the China Scholarship Council.
文摘Magnetic nanopartides have been used as drug delivery vehicles against a number of cancer cells. Most of these theranostic formulations have used solid iron oxide nanoparticles （SIONPs） loaded with chemotherapeutics as nano-carrier formulation for both magnetic resonance imaging （MRI） and cancer therapy. In this study, we applied the dopamine-plus-human serum albumin （HSA） method to modify hollow iron oxide nanoparticles （HIONPs） and encapsuated doxorubicin （DOX） within the hollow porous structure of the nano-carrier. The new delivery system can load more drug than solid iron oxide nanoparticles of the same core size using the same coating strategy. The HIONPs-DOX formulation also has a pH-dependent drug release behaviour. Compared with free DOX, the HIONPs-DOX were more effectively uptaken by the multidrug resistant OVCAR8- ADR cells and consequently more potent in killing drug resistant cancer cells. MRI phantom and cell studies also showed that the HIONPs-DOX can decrease the T2 MRI signal intensity and can be used as a MR/contrast agent while acting as a drug delivery vehicle. For the first time, the dual application of chemo drug transport and MR imaging using the HIONPs-DOX formulation was achieved against both DOX-sensitive and DOX-resistant cancer cells.
文摘Inorganic nanoparticles have been introduced into biological systems as useful probes for in vitro diagnosis and in vivo imaging, due to their relatively small size and exceptional physical and chemical properties. A new kind of color- tunable Gd-Zn-Cu-In-S/ZnS （GZCIS/ZnS） quantum dots （QDs） with stable crystal structure has been successfully synthesized and utilized for magnetic resonance （MR） and fluorescence dual modality imaging. This strategy allows successful fabrication of GZCIS/ZnS QDs by incorporating Gd into ZCIS/ZnS QDs to achieve great MR enhancement without compromising the fluorescence properties of the initial ZCIS/ZnS QDs. The as-prepared GZCIS/ZnS QDs show high T1 MR contrast as well as ＂color-tunable＂ photoluminescence （PL） in the range of 550-725 nm by adjusting the Zn/Cu feeding ratio with high PL quantum yield （QY）. The GZCIS/ZnS QDs were transferred into water via a bovine serum albumin （BSA） coating strategy. The resulting Cd-free GZCIS/ZnS QDs reveal negligible cytotoxicity on both HeLa and A549 cells. Both fluorescence and MR imaging studies were successfully performed in vitro and in vivo. The results demonstrated that GZCIS/ZnS QDs could be a dual-modal contrast agent to simultaneously produce strong MR contrast enhancement as well as fluorescence emission for in vivo imaging.
基金supported by the National Natural Science Foundation of China(Nos.21572042 and 21773052)the Program for Innovative Research Team in Chinese University(No.IRT 1231)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(Nos.LZ16B020002 and LQ17B040002)the Pandeng Plan Foundation of Hangzhou Normal University for Youth Scholars of Materials,Chemistry and Chemical Engineering
文摘A symmetric pillararene-based receptor containing ten triazole units was synthesized.Interestingly,it formed 1:1 complexes instead of 1:2 with different halide anions.This was caused by the cooperative multivalent hydrogen-bond interactions between the triazole protons on one side of the receptor and the halide anion,which changed its structure from pillar to conical.However,by the regulation of the effector F-,it can work like an excavator grapple selectively grasps a PF6-anion.
基金Acknowledgements We thank Dr. M. M. Gottesman at the National Cancer Institute for providing MCF7/MDR cells. We thank Dr. K. R. Williams for manuscript review. This work was supported by the National Institutes of Health （Nos. GM079359 and CA133086） and National Key Scientific Program of China （No. 2011CB911000）, the National Natural Science Foundation of China （NSFC） （Nos. 21325520, J1210040, 20975034 and 21177036）, the Foundation for Innovative Research Groups of NSFC （No. 21221003）, the National Key Natural Science Foundation of China （No. 21135001）, National Instru- mentation Program （No. 2011YQ030124）, the Ministry of Education of China （No. 20100161110011）, and the Hunan Provincial Natural Science Foundation （Nos. 12JJ6012 and 11JJ1002）.
文摘Cancer chemotherapy has been limited by its side effects and multidrug resistance （MDR）, the latter of which is partially caused by drug efflux from cancer cells. Thus, targeted drug delivery systems that can circumvent MDR are needed. Here, we report multifunctional DNA nanoflowers （NFs） for targeted drug delivery to both chemosensitive and MDR cancer cells that circumvented MDR in both leukemia and breast cancer cell models. NFs are self-assembled via potential co-precipitation of DNA and magnesium pyrophosphate generated by rolling circle replication, during which NFs are incorporated using aptamers for specific cancer cell recognition, fluorophores for bioimaging, and doxorubicin （Dox）- binding DNA for drug delivery. NF sizes are tunable （down to N200 nm in diameter）, and the densely packed drug-binding motifs and porous intrastructures endow NFs with a high drug-loading capacity （71.4%, wt/wt）. Although the Dox- loaded NFs （NF-Dox） are stable at physiological pH, drug release is facilitated under acidic or basic conditions. NFs deliver Dox into target chemosensitive and MDR cancer cells, preventing drug efflux and enhancing drug retention in MDR cells. NF-Dox induces potent cytotoxicity in both target chemosensitive cells and MDR cells, but not in nontarget cells, thus concurrently circumventing MDR and reducing side effects. Overall, these NFs are promising tools for circumventing MDR in targeted cancer therapy.
基金supported by the Major State Basic Research Development Program of China(No.2017YFA0205201)the National Natural Science Foundation of China(Nos.81925019,81422023,U1705281,and U1505221)+1 种基金the Fundamental Research Funds for the Central Universities(No.20720190088)the Program for New Century Excellent Talents in University,China(No.NCET-13-0502).
文摘Endo/lysosomal escape and gene release are two critical bottlenecks in gene delivery.Herein,a novel photo-controllable metal-organic frameworks(MOFs)nanoswitch is rationally designed for enhancing small interfering RNA(siRNA)delivery.One single laser triggers the“off-to-on”switching of MOFs nanocomplexes,inducing significant siRNA release accompanied by rapid MOFs dissociation into protonatable 2-methylimidazalo and osmotic rupturing Zn2+ions,which cooperatively contribute to remarkable endo/lysosomal rupture(∼90%).The simultaneous endo/lysosomal rupture and release enable a high spatio-temporal control on RNA interference for effective cancer therapy.Notably,the“off-to-on”switching also activates fluorescence recovery for real-time monitoring siRNA delivery.The nanoswitch could easily be extended to deliver other therapeutic agents(e.g.,DNA,protein,anticancer drug)for overcoming endo/lysosomal entrapment.
基金supported by the National Basic Research Development Program of China(2017YFA0205201 and 2018YFA0107301)the National Natural Science Foundation of China(81422023,81871404,81603015,U1705281,and U1505221)+1 种基金the Fundamental Research Funds for the Central Universities(20720160065,and 20720150141)the Program for New Century Excellent Talents in University,China(NCET-13-0502)
文摘The development of multiple drug resistance(MDR) to chemotherapy and subsequent treatment failures are major obstacles in cancer therapy. An attractive option for combating MDR is inhibiting the expression of P-glycoprotein(P-gp) in tumor cells. Here, we report a novel chemosensitizing agent, XMD8-92,which can down-regulate P-gp. To enhance the specificity of MDR chemotherapy, a promising nanotheranostic micelle system based on poly(ethylene glycol)-blocked-poly(L-leucine)(PEG-b-Leu) was developed to simultaneously carry the anticancer drug doxorubicin, chemosensitizing agent XMD8-92, and superparamagnetic iron oxide nanoparticles(SPIOs). Featured with MDR environmentally responsive dual-targeting capability, controllable drug delivery, and efficient magnetic resonance(MR) imaging characteristics, the prepared nanotheranostics(DXS@NPs) showed outstanding in vitro cytotoxicity on MDR cells(SCG 7901/VCR) with only 53% of cells surviving compared to 90% of DOX-treated cells.Furthermore, efficient tumor inhibition and highly reduced systemic toxicity were exhibited by MDR tumor-bearing mice treated with DXS@NPs. Overall, the environmentally responsive dual-targeting nanotheranostics represent a promising approach for overcoming cancer MDR.
