LAUSR

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, Dox@mP-b-pH, and Dox@mPH-RA were characterized by determining particle size, zeta potential, % DL, EE, Dox release, hemolysis study, and by DSC. The Dox@mPH-RA 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 %. Dox@mPH-RA micelles displayed the highest penetrability and cytotoxicity than free Dox and Dox@mP-b-pH micelles in breast cancer cell lines. Dox@mPH-RA exhibited the highest induction of apoptosis (94.1±3 %) than Dox (52.1±4.5 %), and Dox@mP-b-pH (81.7±3%), and arrested cells in the highest population in G2 and S phase. Dox@mPH-RA increased the t1/2 and Cmax of Dox and demonstrated improved therapeutic efficacy and highest Dox distribution to the tumor. The Dox@mPH-RA 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 Dox@mPH-RA via the combination therapeutic strategy.