Various novel types of supramolecular nanostructures formed by nonamphiphilic azobenzene derivatives,G1 or G2 have been successfully fabricated,where G2 is structurally similar with G1 but an extra phenoxy group is co...Various novel types of supramolecular nanostructures formed by nonamphiphilic azobenzene derivatives,G1 or G2 have been successfully fabricated,where G2 is structurally similar with G1 but an extra phenoxy group is con-nected with the azobenzene motif.Micellar structures can be obtained from the self-assembly of G1,which further transform to large-sized spindle structures;while nanorods can be initially formed by G2,which will gradually ag-gregate to form layered structures with much larger size.Moreover,it is found that upon addition of WP6,which can form inclusion-complex with G1 or G2,separately,the nonamphiphilic G1 and G2 thus converse to supramolecular amphiphiles WP6⊃G1 and WP6⊃G2,respectively.Consequently,both of the above WP6⊃G1 and WP6⊃G2 complexes can further assemble to form supramolecular binary vesicles,which will gradually transform to nanotubes(WP6⊃G1)or well-ordered nanosheets(WP6⊃G2).展开更多
Supramolecular assemblies （PS-b-P4VP （AzoR）） are fabricated by hydrogen-bonding azobenzene derivatives （AzoR） to poly（4-vinyl pyridine） blocks of polystyrene-block-poly（4-vinyl pyridine） （PS-b-P4VP）. PS-b-...Supramolecular assemblies （PS-b-P4VP （AzoR）） are fabricated by hydrogen-bonding azobenzene derivatives （AzoR） to poly（4-vinyl pyridine） blocks of polystyrene-block-poly（4-vinyl pyridine） （PS-b-P4VP）. PS-b-P4VP（AzoR） forms phase separated nanostructures with a period of-75-105 nm. A second length scale structure with a period of 2μm is fabricated on phase separated PS-b-P4VP（AzoR） by laser interference abla- tion. Both the concentration and the substituent of AzoR in PS-b-P4VP（AzoR） affect the laser ablation process. The laser ablation threshold of PS-b-P4VP（AzoR） decreases as the concentration of AzoR increases. In PS-b-P4VP（AzoR） with different substituents （R = CN, H, and CH3）, ablation thresholds follow the trend： PS-b-P4VP（AzoCN）〈 PS-b- P4VP（AzoCH3）〈PS-b-P4VP（AzoH）. This result indicates that the electron donor group （CH3） and the electron acceptor group （CN） can lower the ablation threshold of PS-b-P4VP（AzoR）.展开更多
Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers,which benefits from tumor downstaging.However,the utility of chemotherapeutics alone as a neoadjuvant agent is incapable...Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers,which benefits from tumor downstaging.However,the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence.Herein,a tactical nanomissile(TALE),equipped with a guidance system(PD-L1 monoclonal antibody),ammunition(mitoxantrone,Mit),and projectile bodies(tertiary amines modified azobenzene derivatives),is designed as a neoadjuvant chemo-immunotherapy setting,which aims at targeting tumor cells,and fast-releasing Mit owing to the intracellular azoreductase,thereby inducing immunogenic tumor cells death,and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system.The formed in situ tumor vaccine can recruit and activate antigen-presenting cells,and ultimately increase the infiltration of CD8^(+)T cells while reversing the immunosuppression microenvironment.Moreover,this approach provokes a robust systemic immune response and immunological memory,as evidenced by preventing 83.3%of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model.Collectively,our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.展开更多
基金supported by the National Natural Science Foundation of China (No.21202083)Jiangsu Provincial Natural Science Foundation of China (No.BK20140595).
文摘Various novel types of supramolecular nanostructures formed by nonamphiphilic azobenzene derivatives,G1 or G2 have been successfully fabricated,where G2 is structurally similar with G1 but an extra phenoxy group is con-nected with the azobenzene motif.Micellar structures can be obtained from the self-assembly of G1,which further transform to large-sized spindle structures;while nanorods can be initially formed by G2,which will gradually ag-gregate to form layered structures with much larger size.Moreover,it is found that upon addition of WP6,which can form inclusion-complex with G1 or G2,separately,the nonamphiphilic G1 and G2 thus converse to supramolecular amphiphiles WP6⊃G1 and WP6⊃G2,respectively.Consequently,both of the above WP6⊃G1 and WP6⊃G2 complexes can further assemble to form supramolecular binary vesicles,which will gradually transform to nanotubes(WP6⊃G1)or well-ordered nanosheets(WP6⊃G2).
文摘Supramolecular assemblies （PS-b-P4VP （AzoR）） are fabricated by hydrogen-bonding azobenzene derivatives （AzoR） to poly（4-vinyl pyridine） blocks of polystyrene-block-poly（4-vinyl pyridine） （PS-b-P4VP）. PS-b-P4VP（AzoR） forms phase separated nanostructures with a period of-75-105 nm. A second length scale structure with a period of 2μm is fabricated on phase separated PS-b-P4VP（AzoR） by laser interference abla- tion. Both the concentration and the substituent of AzoR in PS-b-P4VP（AzoR） affect the laser ablation process. The laser ablation threshold of PS-b-P4VP（AzoR） decreases as the concentration of AzoR increases. In PS-b-P4VP（AzoR） with different substituents （R = CN, H, and CH3）, ablation thresholds follow the trend： PS-b-P4VP（AzoCN）〈 PS-b- P4VP（AzoCH3）〈PS-b-P4VP（AzoH）. This result indicates that the electron donor group （CH3） and the electron acceptor group （CN） can lower the ablation threshold of PS-b-P4VP（AzoR）.
基金financially supported by the National Natural Science Foundation of China(82172094)Funds of Sichuan Province for Distinguished Young Scholar(2021JDJQ0037,China)1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYYC08002,China)。
文摘Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers,which benefits from tumor downstaging.However,the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence.Herein,a tactical nanomissile(TALE),equipped with a guidance system(PD-L1 monoclonal antibody),ammunition(mitoxantrone,Mit),and projectile bodies(tertiary amines modified azobenzene derivatives),is designed as a neoadjuvant chemo-immunotherapy setting,which aims at targeting tumor cells,and fast-releasing Mit owing to the intracellular azoreductase,thereby inducing immunogenic tumor cells death,and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system.The formed in situ tumor vaccine can recruit and activate antigen-presenting cells,and ultimately increase the infiltration of CD8^(+)T cells while reversing the immunosuppression microenvironment.Moreover,this approach provokes a robust systemic immune response and immunological memory,as evidenced by preventing 83.3%of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model.Collectively,our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.
基金supported by the National Science Fund for Distinguished Young Scholars(22125804)the National Natural Science Foundation of China(22078155)the Project of Priority Academic Program Development of Jiangsu Higher Education Institutions。
