Somatostatin receptors （SSTRs） were widely expressed in many tumor cells. As a somatostatin analogue, vapreotide （VAP） can be exploited as a modifier for targeting tumor therapy based on its high affinity to SSTR....Somatostatin receptors （SSTRs） were widely expressed in many tumor cells. As a somatostatin analogue, vapreotide （VAP） can be exploited as a modifier for targeting tumor therapy based on its high affinity to SSTR. In this study, we conjugated α-NH2 of exocyclic n-phenylalanine （D-Phe） of vapreotide to N-hydroxysuccinimidyl-PEG2000-DSPE （NHS-PEG-DSPE）, and the resulted DSPE-PEG-VAP was used as a targeting component to construct the targeted micelles for delivering paclitaxel （VAP-M-PTX） through a thin-film hydration method. Similar particle size, zeta potential, drug encapsulation efficiencies, drug release behaviors and hemolysis effects were observed between the targeted micelles （VAP-M-PTX） and the non-targeted micelles （M-PTX）. In MCF-7 cells, significantly higher intracellular fluorescence intensity （1.5-fold） was determined by flow cytometry after incubation of coumarin-6 loaded targeted micelles （VAP-M-Cou） for 3 h compared with non-targeted mieelles （M-Cou）, and similar finding was observed confocal microscopy. Furthermore, in comparison with non-targeted formulations, higher antitumor efficacy and higher drug accumulation were found in MCF-7 tumors in nude mice after intravenous injection of the targeted micelles. In conclusion, we believed that the vapreotide-modified nanomicelles could be a promising targeted nanocarrier for delivering anticancer drugs to the tumors with overexpression of somatostatin receptors.展开更多
基金National Basic Research Program of China(973 Program,Grant No.2013CB932501)NSFC projects(Grant No.81273455 and 81473158)Programs from Ministry of Education(Grant No.NCET-11-0014 and BMU20110263)
文摘Somatostatin receptors （SSTRs） were widely expressed in many tumor cells. As a somatostatin analogue, vapreotide （VAP） can be exploited as a modifier for targeting tumor therapy based on its high affinity to SSTR. In this study, we conjugated α-NH2 of exocyclic n-phenylalanine （D-Phe） of vapreotide to N-hydroxysuccinimidyl-PEG2000-DSPE （NHS-PEG-DSPE）, and the resulted DSPE-PEG-VAP was used as a targeting component to construct the targeted micelles for delivering paclitaxel （VAP-M-PTX） through a thin-film hydration method. Similar particle size, zeta potential, drug encapsulation efficiencies, drug release behaviors and hemolysis effects were observed between the targeted micelles （VAP-M-PTX） and the non-targeted micelles （M-PTX）. In MCF-7 cells, significantly higher intracellular fluorescence intensity （1.5-fold） was determined by flow cytometry after incubation of coumarin-6 loaded targeted micelles （VAP-M-Cou） for 3 h compared with non-targeted mieelles （M-Cou）, and similar finding was observed confocal microscopy. Furthermore, in comparison with non-targeted formulations, higher antitumor efficacy and higher drug accumulation were found in MCF-7 tumors in nude mice after intravenous injection of the targeted micelles. In conclusion, we believed that the vapreotide-modified nanomicelles could be a promising targeted nanocarrier for delivering anticancer drugs to the tumors with overexpression of somatostatin receptors.
