Platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy

Abstract

The preparation of polymer therapeutics capable of controlled release of multiple chemotherapeutic drugs has remained a tough problem in synergistic combination cancer therapy. Herein, a novel dual-drug co-delivery system carrying doxorubicin (DOX) and platinum(IV) (Pt[IV]) was developed. An amphiphilic diblock copolymer, PCL-b-P(OEGMA-co-AzPMA), was synthesized and used as a nanoscale drug carrier in which DOX and Pt(IV) could be packaged together. The copolymers were shell cross-linked by Pt(IV) prodrug via a click reaction. Studies on the in vitro drug release and cellular uptake of the dual-drug co-delivery system showed that the micelles were effectively taken up by the cells and simultaneously released drugs in the cells. Futhermore, the co-delivery polymer nanoparticles caused much higher cell death in HeLa and A357 tumor cells than either the free drugs or single-drug-loaded micelles at the same dosage, exhibiting a synergistic combination of DOX and Pt(IV). The results obtained with the shell cross-linked micelles based on an anticancer drug used as a cross-linking linkage suggested a promising application of the micelles for multidrug delivery in combination cancer therapy.

<p>Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis</p>

“…The amphiphilic micelles shaped in aqueous condition including a core-shell structure stock insolubility drugs by the hydrophobic core and keep a stable structure in an aqueous condition through the hydrophilic group. 33 Furthermore, the micellar delivery system may provide more drug accumulated in bone tissues due to its nanosize effect. 34 Therefore, it represents a more effective and safe treatment compared to repeated local injections.…”

Thermoresponsive Nanogels Based on Different Polymeric Moieties for Biomedical Applications

“…Lutz et al synthesized copolymers of MEO2MA and OEGMA via atom transfer radical polymerization and observed possible control of LCST between 26 and 90 °C by altering the monomer compositions [ 152 ]. Consequently, a large number of different types of polymers [ 153 , 154 , 155 ], micelles [ 156 , 157 ], vesicles [ 158 ], micro/nanogels [ 159 ], and smart POEGMA-based hydrogels [ 160 ] have been synthesized and investigated.…”

Dual-responsive dithio-polydopamine coated porous CeO₂ nanorods for targeted and synergistic drug delivery

“…The content of the remaining DOX was calculated according to a calibration curve. The loading content of Lac-PDS/DOX@CeONRs was calculated by the following equation: 31…”

“…[26][27][28][29] However, there are only a few reports on fabricating both responsive and targeted polymers for synergistic drug delivery. 30,31 Polydopamine (PDA)-based substrate-independent coating, due to its adhesive property, 32 has been comprehensively applied in nanomedicine for drug delivery systems (DDS). [33][34][35][36] One valuable feature of PDA lies in its chemical structure that incorporates many functional groups such as catechol, amine, and imine, which further realize the emergence of diverse hybrid materials.…”