Synthesis of Reduction-Sensitive Brush-Arm Star Polymers via Combined Ring-Opening Metathesis Polymerization–Atom Transfer Radical Polymerization and Controlled-Release Properties

Mild reaction conditions and excellent functional group tolerance make ring-opening metathesis polymerization (ROMP) a widely used technique to synthesize functional materials. In this work, we used ROMP and atom transfer radical polymerization (ATRP) to prepare a reduction-sensitive brush-arm star polymer (BASP) drug carrier by a one-pot method and further conducted in vitro studies. First, a bifunctional norbornene-based ATRP initiator NB-Br and a reduction-sensitive dinorbornene cross-linker (DNC) were synthesized. Subsequently, NB-Br was subjected to ATRP using the hydrophilic monomer oligoethylene glycol monomethyl ether methacrylate (OEGMA) at different polymerization times to obtain the norbornenyl macromonomer NB-P(OEGMA)n with different degrees of polymerization. In the same reaction flask, NB-P(OEGMA)n underwent an ROMP reaction to generate a brush-shaped polymer. Next, DNC was added to the reaction flask, and the reaction was continued to obtain BASP. This one-pot method could successfully be used to achieve the transformation of the macromonomer to the brush-shaped polymer and subsequently to the star polymer. In vitro biological experiments demonstrated that BASP micelles exhibited reduction-triggered cleavage of disulfide bonds and degradation of polymers after coculture with 10 mM glutathione, promoting the release of intracellular doxorubicin and achieving the controlled release of drugs. We expect the findings of our study to serve as an efficient synthetic strategy to prepare carriers for biomedical applications.