Abstract
Although stimuli-responsive co-delivery systems of chemotherapy drugs and microRNA (miRNA) can serve as a promising treatment strategy for cancer, to our best knowledge, pH-responsive nanocarriers for the codelivery of chemical drugs and microRNAs (miRNAs) have not yet been reported. In this study, we synthesized doxorubicin (DOX)-tethered linear polyethylenimine (LPEI) conjugates linked via a pH-responsive hydrazone bond (LPEI-HZ-DOX) for the synchronous delivery of DOX and miRNA-34a. The free DOX was successfully released from the LPEI-HZ-DOX conjugates at acidic pH, which provided selective toxicity against cancer cells in a pH-sensitive manner. The resulting LPEI-HZ-DOX conjugates formed nano-sized complexes with chemically modified long-chain miRNAs with a size of ∼200 nm, which exhibited synergistic toxicity and anti-proliferation activity against PC-3 cancer cells. This platform of cationic conjugates with high biocompatibility could serve as a pH-sensitive in vitro system for gene and drug delivery.
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