Plasmonic Nano-Polymersomes for Pulsed Laser-Triggered Intracellular Cargo Release

Abstract Polymersomes are synthetic vesicles capable of encapsulating both hydrophilic and hydrophobic cargo, making them attractive candidates for drug delivery applications. The inherent stability of polymer vesicles, such as poly(butadiene)33-b-poly(ethylene oxide)20 polymersomes, is advantageous for cargo retention, but can also make controlled cargo release a challenge. In this work, nano-polymersomes containing membrane-incorporated gold nanoparticles (AuNPs) were investigated as a pulsed laser-responsive delivery platform for intracellular cargo release. Hydrophobic AuNPs embedded within the membrane serve as plasmonic photosensitizers, rendering the vesicles responsive to 532 nm picosecond and nanosecond laser irradiation. To evaluate their utility for intracellular cargo release, doxorubicin was encapsulated within the aqueous core of the polymersomes. Polymersomes were evaluated for stability in common cell culture buffers and demonstrated efficient internalization with negligible cytotoxicity in NIH 3T3 cells. Following irradiation, doxorubicin-loaded polymersomes produced a significant reduction in cell viability, whereas control groups exhibited minimal toxicity. These findings demonstrate the potential of AuNP-polymersomes as candidates for externally triggered drug delivery vehicles for laser-mediated intracellular cargo release.