In vitro targeting efficiency evaluation of reduction-responsive co-loaded doxorubicin/siRNA nanoparticles

【作者】 王钰； 张学农；

【Author】 Yu Wang;Xue-nong Zhang;Department of Pharmaceutics, College of Phaemaceutical Science, Soochow University;

【机构】 苏州大学药学院；

【摘要】 Antitumor agents play important roles in cancer treatment. Silencing specific gene to suppress tumor proliferation or metastasis was widely investigated by researchers. Thus combining cytotoxic effect with gene silencing effect would be a choice to improve the efficacy of tumor therapy. In this study, a reduction-responsive nanoparticle(HA-PLA-NP) was designed for the co-delivery of DOX and siRNA. DOX was loaded into HA-PLA-NP with encapsulation efficiency of(86.93±8.91)% and drug loading of(4.17±0.68)%. The best N:P ratio is 6:1. HA-PLA/DOX-siRNA-NP showed a hydrodynamic diameter of(167.3±9.9) nm and negative zeta potential of-(15.5±1.4) m V at the optimal ratio of PLA:HA(1:3). HA could shield the positive charge of PLA-NP in blood circulation, be degraded by HAase at tumor site and interact with CD44 receptor which enhanced cellular uptake of NP. Because of proton effect of PLL and disulfide bonds’ responsiveness to GSH in cytoplasm, HA-PLA/DOX-siRNA-NP escaped from endolysosomes successfully and released payloads rapidly. Therefore, the reduction-responsive NP modified with HA has great potential to act as co-delivery system for antitumor agents and siRNA.更多还原

【Abstract】 Antitumor agents play important roles in cancer treatment. Silencing specific gene to suppress tumor proliferation or metastasis was widely investigated by researchers. Thus combining cytotoxic effect with gene silencing effect would be a choice to improve the efficacy of tumor therapy. In this study, a reduction-responsive nanoparticle(HA-PLA-NP) was designed for the co-delivery of DOX and siRNA. DOX was loaded into HA-PLA-NP with encapsulation efficiency of(86.93±8.91)% and drug loading of(4.17±0.68)%. The best N:P ratio is 6:1. HA-PLA/DOX-siRNA-NP showed a hydrodynamic diameter of(167.3±9.9) nm and negative zeta potential of-(15.5±1.4) m V at the optimal ratio of PLA:HA(1:3). HA could shield the positive charge of PLA-NP in blood circulation, be degraded by HAase at tumor site and interact with CD44 receptor which enhanced cellular uptake of NP. Because of proton effect of PLL and disulfide bonds’ responsiveness to GSH in cytoplasm, HA-PLA/DOX-siRNA-NP escaped from endolysosomes successfully and released payloads rapidly. Therefore, the reduction-responsive NP modified with HA has great potential to act as co-delivery system for antitumor agents and siRNA.更多还原