Photoresponsive polymersomes for nanoencapsulation of multiple cargoes as a potential theranostic strategy

Inspired by the cell's membrane architecture, self-assembling amphiphilic copolymers in polymersomes can form biomimetic, compartmentalized, bilayered, and versatile structures through supramolecular interactions, enabling the simultaneous co-encapsulation of hydrophilic and hydrophobic cargo. This approach protects cargo from the surrounding media and modulates cargo release via stimuli-responsive mechanisms, such as light. This work reports on a photosensitive polymersome derived from an amphiphilic random copolymer based on poly(ethylene-alt-maleic anhydride) and a 2-nitrobenzyl alcohol light-responsive moiety. Fourier-transform infrared spectroscopy, magnetic nuclear resonance spectroscopy, and thermal analysis were used to characterize the resulting amphiphilic copolymer. UV-light-responsive polymersomes were successfully assembled with a size of 80.38 ± 1.57 nm, a ζ-potential of -50.9 ± 0.8 mV, and a bilayer thickness of 3.5 ± 1.2 nm, as confirmed by cryo- and transmission-electron microscopy. Moreover, it assembled biotinylated polymersomes with similar physicochemical properties for the targeted delivery of cargo to cancer cells. It encapsulated 5-fluorouracil (5-FU) and rhodamine-B (Rh-B) into polymersomes with high encapsulation efficiency and loading capacity as cargo models of different natures, and gold nanoparticles and magnetic nanoparticles/5-FU as a potential theranostic strategy. Polymersomes demonstrated high biocompatibility, and the encapsulated 5-FU exerted cytotoxicity after 24 h of treatment following 5 minutes of UV-triggered cargo release, positioning them as stimuli-responsive nanosystems for electromagnetic irradiation-triggered drug delivery.