Triple Functional AB₂ Unit-Modulated Facile Preparation of Bioreducible Hyperbranched Copolymers

Abstract

Facile preparation of hyperbranched polymers (HPs) has been advanced tremendously by the use of either various multifunctional agent-mediated controlled living radical polymerizations or a highly reactive AB x unit-modulated self-stepwise polymerizations. However, it remains, to our knowledge, a significant challenge to prepare HPs with simultaneously precisely controlled degree of branching (DB) and biorelevant signal-triggered degradation property for controlled release applications due to the respective limitations of the aforementioned two strategies. For this purpose, a triple functional AB2 unit, A-SS-B2 chain transfer agent (AB2 CTA), that integrates the merits of both multifunctional agents and highly reactive AB x units was designed and synthesized successfully to include a disulfide bond for reduction-triggered polymer degradation toward promoted intracellular release of encapsulated cargoes, a trithiocarbonate group for a universal reversible addition-fragmentation chain transfer (RAFT) polymerization of any vinyl-based monomer, and three terminal groups consisting of one azide and two alkyne functions for the generation of hyperbranched topology via a self-click coupling-based polymerization. A subsequent self-click polymerization of the resulting AB2 CTA by click coupling in the presence of CuSO4·5H2O and sodium ascorbate (NaVc) generated a hyperbranched polymer template (HPT) with precisely modulated DB and a plurality of CTA units for a universal reversible addition-fragmentation chain transfer (RAFT) polymerization of any vinyl-containing monomer. The HPT was next used as a multimacro-CTA for RAFT polymerization of a typical hydrophilic monomer, oligo­(ethylene glycol) monomethyl ether methacrylate (OEGMA), to demonstrate the potential of this HPT for a robust and facile production of bioreducible hyperbranched polymers for controlled release applications. The synthesized HPT-4-POEGMA can form unimolecular micelles with enhanced stability due to the hyperbranched structure, and the size of micelles varied in the range from 82.4 to 140.3 nm by a modulation of the molar feed ratio of monomer to HPT and polymerization time. More importantly, HPT-POEGMA micelles incubated with 10 mM glutathione (GSH) showed reduction-triggered cleavage of the disulfide links and polymer degradation for promoted intracellular doxorubicin (DOX) release and enhanced therapeutic efficiency. Taken together, this triple functional AB2 CTA provided a powerful means for the facile preparation of bioreducible hyperbranched polymers with precisely controlled DB for controlled release applications.

A cyclic brush zwitterionic polymer based pH-responsive nanocarrier-mediated dual drug delivery system with lubrication maintenance for osteoarthritis treatment

“…The DLC and EE of BB@Cur@LXP and CB@Cur@LXP were 21.7% and 77.8%, 27.4% and 84%, respectively. Encouragingly, both CB and BB reported here show higher drug loading efficiency compared to the previously reported drugs of polymer micelles with different morphologies by physical entrapment 14,43,49–56 and drugs of brush polymers by chemical binding 57,58 (Fig. 3a).…”

Facile Synthesis of Hyperbranched Copolymers via an [A2 + B3] Click Polymerization Synthesized Reducible Hyperbranched Template

“…In addition, our previous study has confirmed variation of the DB of HPT via modulation of the reaction time for HPT synthesis. 34 A polymer panel of HPT-P(α-OEGMA) with three different MWs (Table 1) was synthesized by readily varying the polymerization time.…”