Surface plasmon resonance(SPR) nanosensors based on metallic nanohole arrays have been widely reported to detect binding interactions in biological specimens. A simple and effective method for constructing nanoscale a...Surface plasmon resonance(SPR) nanosensors based on metallic nanohole arrays have been widely reported to detect binding interactions in biological specimens. A simple and effective method for constructing nanoscale arrays is essential for the development of SPR nanosensors. In this work, we report a one-step method to fabricate nanohole arrays by thermal nanoimprinting in the matrix of IPS(Intermediate Polymer Stamp). No additional etching process or supporting substrate is required. The preparation process is simple, time-saving and compatible for roll-to-roll process, potentially allowing mass production. Moreover, the nanohole arrays were integrated into detection platform as SPR sensors to investigate different types of biological binding interactions. The results demonstrate that our one-step method can be used to efficiently fabricate large-area and uniform nanohole arrays for biochemical sensing.展开更多
Temozolomide (TMZ) is a clinically approved drug for glioblastoma (GBM) therapy. However, as a result of methylguanine-DNA-methyltransferase (MGMT), which is able to repair damaged DNA-damage repairing, TMZ usually yi...Temozolomide (TMZ) is a clinically approved drug for glioblastoma (GBM) therapy. However, as a result of methylguanine-DNA-methyltransferase (MGMT), which is able to repair damaged DNA-damage repairing, TMZ usually yields unsatisfactory therapeutic effects. Small interfering RNA (siRNA) is a potential alteration tool for sensitivity of TMZ by targeting DNA repair enzymes. However, a suitable TMZ and siRNA codelivery system that can effectively and actively co-deliver siRNA/TMZ into the brain tumor is lacking. In this study, we constructed an angiopep-2 decorated polymersomal delivery system to co-deliver TMZ/siRNA for synergistic GBM therapy. This targeted polymersomal nanomedicine not only enhanced the circulation time of siRNA/TMZ in blood but also improved their blood-brain barrier (BBB) crossing and GBM targeting ability. Moreover, when we co-administered siRNAs specific to retinoblastoma binding protein 4 (RBBP4) together with TMZ in GBM cells, these RBBP4- specific siRNA (siRBBP4) modulated the sensitivity of TMZ by regulating MGMT, and thus showed a powerful synergistic anti-tumor effect. We demonstrated that angiopep-2 decorated polymersomal siRBBP4/TMZ co-loaded nanomedicines are capable of inhibiting tumor growth and significantly improved life expectancy of orthotropic GBM bearing mice. Overall, our study suggests that such a polymersomal TMZ/siRNA codelivery system provides a robust and potent nanoplatform for targeted GBM chemo-RNAi therapy.展开更多
基金financially supported by the National Natural Science Foundation of China (31430061, 61401149, and U1604177)Ministry of Agriculture of China (2016ZX08009-003)the Program of China’s 1000-talents Plan
文摘Surface plasmon resonance(SPR) nanosensors based on metallic nanohole arrays have been widely reported to detect binding interactions in biological specimens. A simple and effective method for constructing nanoscale arrays is essential for the development of SPR nanosensors. In this work, we report a one-step method to fabricate nanohole arrays by thermal nanoimprinting in the matrix of IPS(Intermediate Polymer Stamp). No additional etching process or supporting substrate is required. The preparation process is simple, time-saving and compatible for roll-to-roll process, potentially allowing mass production. Moreover, the nanohole arrays were integrated into detection platform as SPR sensors to investigate different types of biological binding interactions. The results demonstrate that our one-step method can be used to efficiently fabricate large-area and uniform nanohole arrays for biochemical sensing.
基金This research was funded by China’s National Key Technologies R&D Programs(2018YFA0209800)National Natural Science Founda tion of China(NSFC 52073079,31800841,32071388,and U1804139)+2 种基金Key Research Program in Colleges and Universities of Henan Province(19zx006)Program of Technology Innovation Team in Colleges and Universities of Henan Province(21IRTSTHN028)NHMRC Investi-gator Grant.
文摘Temozolomide (TMZ) is a clinically approved drug for glioblastoma (GBM) therapy. However, as a result of methylguanine-DNA-methyltransferase (MGMT), which is able to repair damaged DNA-damage repairing, TMZ usually yields unsatisfactory therapeutic effects. Small interfering RNA (siRNA) is a potential alteration tool for sensitivity of TMZ by targeting DNA repair enzymes. However, a suitable TMZ and siRNA codelivery system that can effectively and actively co-deliver siRNA/TMZ into the brain tumor is lacking. In this study, we constructed an angiopep-2 decorated polymersomal delivery system to co-deliver TMZ/siRNA for synergistic GBM therapy. This targeted polymersomal nanomedicine not only enhanced the circulation time of siRNA/TMZ in blood but also improved their blood-brain barrier (BBB) crossing and GBM targeting ability. Moreover, when we co-administered siRNAs specific to retinoblastoma binding protein 4 (RBBP4) together with TMZ in GBM cells, these RBBP4- specific siRNA (siRBBP4) modulated the sensitivity of TMZ by regulating MGMT, and thus showed a powerful synergistic anti-tumor effect. We demonstrated that angiopep-2 decorated polymersomal siRBBP4/TMZ co-loaded nanomedicines are capable of inhibiting tumor growth and significantly improved life expectancy of orthotropic GBM bearing mice. Overall, our study suggests that such a polymersomal TMZ/siRNA codelivery system provides a robust and potent nanoplatform for targeted GBM chemo-RNAi therapy.
