Synthesis of Amphiphilic Block Polyphosphoester and Exploring Its Potential in Reduction-Responsive Drug Release

In this work, a reduction-responsive amphiphilic block polyphosphoester was synthesized via one-pot sequential organocatalytic ring-opening polymerization of 2-butoxy-1,3,2-dioxaphospholane 2-oxide (BEP) and 2-(but-3-en-1-yloxy)-1,3,2-dioxaphospholane 2-oxide (BenEP), followed by postpolymerization modification through click reaction with 2-mercaptoethanol and esterification with dithiodipropionic anhydride, respectively. The as-prepared PBEP-b-PBenEP-SS-COOH, abbreviated as PBBS, can self-assemble into well-dispersed spherical nanoparticles with an average size of about 75 nm in aqueous solution, and the nanoparticles exhibit glutathione (GSH)-triggered disassembly, which can be a promising antitumor drug carrier. Paclitaxel (PTX) encapsulation and in vitro responsive release results confirm that the PTX-loaded PBBS nanoparticles (PTX@PBBS) with drug loading content of 4.3% have an increased average size of 138 nm and exhibit a promising drug release feature with approximately 80% of PTX within 24 h incubation in the medium with 10 mM GSH. In addition, both cytotoxicity and intracellular uptake investigations demonstrate that the PBBS nanoparticles have a good biocompatibility, while PTX@PBBS can be internalized by tumor cells and efficiently release the anticancer drug PTX to inhibit the proliferation of tumor cells.