Pegylated and nanoparticle-conjugated sulfonium salt photo triggers necrotic cell death

Photodynamic therapy (PDT) processes involving the production of singlet oxygen face the issue of oxygen concentration dependency. Despite high oxygen delivery, a variety of properties related to metabolism and vascular morphology in cancer cells result in hypoxic environments, resulting in limited effectiveness of such therapies. An alternative oxygen-independent agent whose cell cytotoxicity can be remotely controlled by light may allow access to treatment of hypoxic tumors. Toward that end, we developed and tested both polyethylene glycol (PEG)-functionalized and hydrophilic silica nanoparticle (SiNP)-enriched photoacid generator (PAG) as a nontraditional PDT agent to effectively induce necrotic cell death in HCT-116 cells. Already known for applications in lithography and cationic polymerization, our developed oxygen-independent PDT, whether free or highly monodispersed on SiNPs, generates acid when a one-photon (1P) or two-photon (2P) excitation source is used, thus potentially permitting deep tissue treatment. Our study shows that when conjugated to SiNPs with protruding amine functionalities (SiNP–PAG9), such atypical PDT agents can be effectively delivered into HCT-116 cells and compartmentalize exclusively in lysosomes and endosomes. Loss of cell adhesion and cell swelling are detected when an excitation source is applied, suggesting that SiNP–PAG9, when excited via near-infrared 2P absorption (a subject of future investigation), can be used as a delivery system to selectively induce cell death in oxygen-deprived optically thick tissue.