Linear polyethyleneimine-doxorubicin conjugate for pH-responsive synchronous delivery of drug and microRNA-34a

• Published in: Macromolecular research Vol. 23; no. 5; pp. 449 - 456
• Main Authors: Jung, Hyosook, Kim, Seung An, Lee, Eunjoo, Mok, Hyejung
• Format: Journal Article
• Language: English
• Published: Seoul The Polymer Society of Korea 01.05.2015; 한국고분자학회
• Subjects: Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Complex Fluids and Microfluidics; Nanochemistry; Nanotechnology; Physical Chemistry; Polymer Sciences; Soft and Granular Matter; 고분자공학; microRNA; doxorubicin; co-delivery system; linear polyethyleneimine; pH-responsive
• ISSN: 1598-5032; 2092-7673
• DOI: 10.1007/s13233-015-3060-y

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.