Polymeric micelles of a copolymer composed of all-trans retinoic acid, methoxy-poly(ethylene glycol), and b-poly(N-(2 hydroxypropyl) methacrylamide) as a doxorubicin-delivery platform and for combination chemotherapy in breast cancer

Delivery of combination chemotherapeutic agents to the tumor via nanovesicles has the potential for superior tumor suppression and reduced toxicity. Herein, we prepare a block copolymer (mPH-RA) composed of methoxy-poly(ethylene glycol) (mPEG), b-poly(N-(2 hydroxypropyl) methacrylamide) (pHPMA), and all-trans retinoic acid (ATRA) by conjugating ATRA to the pre-formed copolymer, mPEG-b-pHPMA(mP-b-pH). Doxorubicin-loaded micelles, [email protected]b-pH, and [email protected] were characterized by determining particle size, zeta potential, % DL, EE, Dox release, hemolysis study, and by DSC. The [email protected] micelles (mPH-RA: Dox ratios of 10:0.5–2) displayed nano-size (36–45 nm), EE. 26–74%, and DL. 2.9–5.6%. [email protected] micelles displayed the highest penetrability and cytotoxicity than free Dox and [email protected]b-pH micelles in breast cancer cell lines. [email protected] exhibited the highest induction of apoptosis (94.1 ± 3%) than Dox (52.1 ± 4.5%), and [email protected]b-pH (81.7 ± 3%), and arrested cells in the highest population in G2 and S phase. [email protected] increased the t1/2 and Cmax of Dox and demonstrated improved therapeutic efficacy and highest Dox distribution to the tumor. The [email protected] increased the levels of apoptosis markers, caspase 3, 7, Ki-67, and caused the highest DNA fragmentation. The presence of RA improved the micelles' physicochemical properties, Dox-loading ability, and the therapeutic potential in [email protected] via the combination therapeutic strategy.