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Abstract
Context: Nanoparticles (NPs) have been widely used as carriers to deliver siRNA and chemotherapeutic agents. Bcl-2 siRNA has been widely used to induce cancer cell apoptosis, and doxorubicin (Dox) can destroy cancer cells by binding with cancer cell DNA.
Objective: To investigate the therapeutic effect on lung cancer of simultaneously delivering Dox and Bcl-2-siRNA using epidermal growth factor (EGF) modified monomethoxy (polyethylene glycol)-poly (D, L-lactide-co-glycolide)-poly(L-lysine) (mPEG-PLGA-PLL, PEAL) NPs (EGF-PEAL).
Methods: EGF-PEAL NPs were characterized with respect to size, zeta potential and morphology. Cytotoxicity and drug (or siRNA) loading capacity of EGF-PEAL NPs were analyzed. Cellular uptake, drug release profile, cell killing effects of Dox and Bcl-2-siRNA-loaded EGF-PEAL NPs were assessed. Biodistribution and therapeutic effects of Dox and Bcl-2-siRNA EGF-PEAL NPs were evaluated in H1299 tumor-bearing mice.
Results and discussion: EGF-PEAL NPs or PEAL NPs had nearly negligible cytotoxicity toward H1299 cells. Dox and Bcl-2-siRNA gradually released from EGF-PEAL NPs and exhibited sustained release patterns. Dox and Bcl-2-siRNA-loaded NPs were taken up by cells and induced the apoptosis of H1299 cells more effectively than using Dox or Bcl-2 siRNA alone. With the intravenous injection of PEAL NPs into H1299 xenografted mice, we found that combination treatment suppressed lung cancer growth and reduced Bcl-2 expression in tumor tissue, and EGF-PEAL NPs concentrated in lung tumor much more than non-targeted PEAL NPs.
Conclusion: We conclude that co-delivery of Dox and Bcl-2-siRNA by tumor-targeted EGF-PEAL NPs could significantly inhibit lung cancer growth.
Supplementary material available on line