Multivalent methionine-functionalized biocompatible block copolymers for targeted small interfering RNA delivery and subsequent reversal effect on adriamycin resistance in human breast cancer cell line MCF-7/ADR.

BACKGROUND: Cationic polymers are outstanding representatives of the most efficient small interfering RNA (siRNA) vectors. Low cytotoxicity and siRNA protecting effect can be obtained with these cationic polymers via a variety of structural modifications. Nevertheless, the gap between their efficiency and the requirement for therapeutic processes is still noticeable.

METHODS: A cationic polymer vector was synthesized via the copolymerization of N-(1,3-dihydroxy propan-2-yl)methacrylamide (DHPMA) and N-(3-aminopropyl)methacrylamide (APMA).

RESULTS: APMA provides amine functionality that allows the conjugation of guanidine and methionine groups. Attributed to the hydroxy groups of DHPMA, the synthesized guanidine and methionine grafted DHPMA-b-APMA block copolymer (mDG) is water soluble and has good biocompatibility. The obtained mDG has high zeta potential, narrow molecular weight distribution, better membrane-penetrating ability, high transfection efficiency, tumor cell targeting ability and high stability.

CONCLUSIONS: The synthesized polymer vector can deliver siRNA molecules into tumor cells and then reverse drug resistance by down regulation of P-glycoprotein mRNA expression.