Details

Autor(en) / Beteiligte

• Chen, Weicai
• Yuan, Yuanyuan
• Cheng, Du
• Chen, Jifeng
• Wang, Lu
• Shuai, Xintao

Titel

Co-Delivery of Doxorubicin and siRNA with Reduction and pH Dually Sensitive Nanocarrier for Synergistic Cancer Therapy

Ist Teil von

• Small (Weinheim an der Bergstrasse, Germany), 2014-07, Vol.10 (13), p.2678-2687

Ort / Verlag

Germany: Blackwell Publishing Ltd

Erscheinungsjahr

2014

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• Drug resistance is the greatest challenge in clinical cancer chemotherapy. Co‐delivery of chemotherapeutic drugs and siRNA to tumor cells is a vital means to silence drug resistant genes during the course of cancer chemotherapy for an improved chemotherapeutic effect. This study aims at effective co‐delivery of siRNA and anticancer drugs to tumor cells. A ternary block copolymer PEG‐PAsp(AED)‐PDPA consisting of pH‐sensitive poly(2‐(diisopropyl amino)ethyl methacrylate) (PDPA), reduction‐sensitive poly(N‐(2,2′‐dithiobis(ethylamine)) aspartamide) PAsp(AED), and poly(ethylene glycol) (PEG) is synthesized and assembled into a core‐shell structural micelle which encapsulated doxorubicin (DOX) in its pH‐sensitive core and the siRNA‐targeting anti‐apoptosis BCL‐2 gene (BCL‐2 siRNA) in a reduction‐sensitive interlayer. At the optimized size and zeta potential, the nanocarriers loaded with DOX and BCL‐2 siRNA may effectively accumulate in the tumor site via blood circulation. Moreover, the dual stimuli‐responsive design of micellar carriers allows microenviroment‐specific rapid release of both DOX and BCL‐2 siRNA inside acidic lysosomes with enriched reducing agent, glutathione (GSH, up to 10 mm). Consequently, the expression of anti‐apoptotic BCL‐2 protein induced by DOX treatment is significantly down‐regulated, which results in synergistically enhanced apoptosis of human ovarian cancer SKOV‐3 cells and thus dramatically inhibited tumor growth. A dually reduction‐ and pH‐sensitive nanocarrier for co‐delivery of an anticancer drug and siRNA is described. The nanocarrier rapidly releases siRNA and the drug inside lysosomes of cancer cells. The two co‐delivered therapeutic agents act synergistically to suppress tumor growth in mice.