Journal
JOURNAL OF PHYSICAL CHEMISTRY C
Volume 120, Issue 39, Pages 22375-22387Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jpcc.6b06759
Keywords
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Funding
- National Natural Science Foundation of China [31271028, 31570984]
- International Cooperation Fund of the Science and Technology Commission of Shanghai Municipality [15540723400]
- Open Foundation of State Key Laboratory for Modification of Chemical Fibers and Polymer Materials [LK1416]
- Chinese Universities Scientific Fund [CUSF-DH-D-2014019]
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The combination of chemotherapy and gene therapy could induce the enhanced therapeutic efficacy in the cancer therapy. To achieve this goal, a new mesoporous silica nanoparticles (MSNs)based codelivery system was developed for targeted simultaneous delivery of doxorubicin (DOX) and Bcl-2 small interfering RNA (siRNA) into breast cancer cells. The multifunctional MSNs (MSNs-PPPFA) were prepared by modification of polyethylenimine polylysine copolymers (PEI-PLL) via the disulfide bonds, to which a targeting ligand folate-linked poly(ethylene glycol) (FA-PEG) was conjugated. The multifunctional MSNs-PPPFA nanocarrier has the ability to encapsulate DOX into the mesoporous channels of MSNs, while simultaneously carrying siRNA via electrostatic interaction between cationic MSNs-PPPFA and anionic siRNA. The resulting MSNs-PPPFA nanoparticles were characterized with various techniques. The drug release results reveal that DOX released from DOX-loaded MSNs-PPPFA are both pH- and redox-responsive, and the results of cell viability and hemolysis assays show that the functional nanocarrier has excellent biocompatibility. Importantly, the folate-conjugated MSNs-PPPFA showed significantly enhanced intracellular uptake in the folate receptor overexpressed MDA-MB-231 breast cancer cells than nontargeted counterparts and thus results in more DOX and siRNA being codelivered into the cells. Furthermore, the delivery of Bcl-2 siRNA obviously downregulate the Bcl-2 protein expression, and thus targeted codelivery of DOX and Bcl-2 siRNA by DOX@MSNsPPPFA/Bd-2 siRNA in MDA-MB-231 cells could induce remarkable cell apoptosis as indicated by the results of cell viability and cell apoptosis assays. These results indicate that the constructed DOX@MSN5-PPPFA/Bcl-2 siRNA codelivery system is promising for targeted treatment of breast cancer.
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