Regulating Cargo Delivery using Stimuli-Responsive Polymersomes: Membrane Features Drive Antitumor Performance

The permeability and responsiveness of polymer membranes are absolutely relevant in the designing of polymersomes for cargo delivery. We have accordingly correlated structural features, permeability and responsiveness of doxorubicin-loaded (DOX-loaded) nonresponsive and stimuli-responsive polymersomes with their in vivo antitumor performance. Polymer vesicles were produced using amphiphilic block copolymers containing a hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) segment linked to poly[N-(4-isopropylphenylacetamide)ethyl methacrylate] (PPPhA, nonresponsive block), poly[4-(4,4,5,5-tetra-methyl-1,3,2-dioxaborolan-2-yl)benzyl methacrylate] (PbAPE, reactive oxygen species-responsive block) or poly[2-(diisopropylamino)ethyl methacrylate] (PDPA, pH-responsive block). The PDPA-based polymersomes demonstrated outstanding biological performance with antitumor activity notably enhanced compared to the counterparts as attribute to a fast triggered DOX release at acidic tumor environments and polymersome disassembly at pH < 6.8.