Engineering Cross-Linkable Plasmonic Vesicles for Synergistic Chemo-Photothermal Therapy Using Orthogonal Light Irradiation

Plasmonic vesicles combine the advantages of polymersomes and physiochemical properties of inorganic nanoparticles, exhibiting promising applications in theranostic nanovectors. However, although many of these plasmonic vesicles have been engineered as photothermal therapy (PTT) agents and drug carriers, they undergo structural destruction due to localized surface plasmon resonance (LSPR) effect. Notably, the disassembly of plasmonic vesicles leads to the burst release of encapsulated payloads and drastically decrease therapeutic efficacy. Herein, we report the fabrication of plasmonic vesicles that can be tracelessly cross-linked under 410 nm blue light irradiation, which can effectively avoid being disassembled when localized heat generation under light irradiation (e.g., 560 nm). Amphiphilic hybrid gold nanoparticles (AuNPs) functionalized with hydrophilic poly(ethylene oxide) (PEO) and hydrophobic poly(2-((((2-nitrobenzyl)oxy)carbonyl)amino)ethyl methacrylate) (PNBOC) blocks were synthesized via ligand exchange process. The resulting amphiphilic AuNPs self-assemble into plasmonic vesicles capable of simultaneously carrying hydrophobic paclitaxel (PTX) and hydrophilic doxorubicin hydrochloride (DOX) drugs. Upon 410 nm blue light irradiation, primary amine moieties are generated due to the deprotection of NBOC moieties that subsequently undergo inter/intrachain amidation reactions, concurrently cross-linking and permeabilizing the vesicles. As such, the release of encapsulated PTX and DOX drugs could be actuated. Interestingly, the irradiated vesicles with highly densely packed AuNPs within the cross-linked bilayers generate localized high heat and can thus be used for PTT agents due to the LSPR effect of AuNPs under photoirradiation (e.g., 560 nm). Moreover, the hybrid vesicles present good X-ray attenuation capability and can be potentially used for computed tomography (CT) contrast agents. The fabrication of cross-linked plasmonic vesicle-based synergistic chemo-photothermal therapy agents using orthogonal light irradiation opens an avenue to explore new theranostic nanovehicles.