title: Pegylated and nanoparticle-conjugated sulfonium salt photo triggers necrotic cell death.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Central Florida, Orlando, FL, USA.
authors.forename: Alaa A
authors.initials: AA
authors.lastname: Fadhel
authors.affiliation: Department of Chemistry, University of Central Florida, Orlando, FL, USA.
authors.forename: Xiling
authors.initials: X
authors.lastname: Yue
authors.affiliation: Department of Chemistry, University of Central Florida, Orlando, FL, USA.
authors.forename: Ebrahim H
authors.initials: EH
authors.lastname: Ghazvini Zadeh
authors.affiliation: Institute of Physics NASU, Kiev, Ukraine.
authors.forename: Mykhailo V
authors.initials: MV
authors.lastname: Bondar
authors.affiliation: Department of Chemistry and Environmental Science, College of Science and Liberal Arts, New Jersey Institute of Technology, University Heights, Newark, NJ, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Belfield
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D045325:HCT116 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D053758:Nanoparticles / Q000737:chemistry*; D009336:Necrosis; D010100:Oxygen / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods; D017785:Photons; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry; D026082:Singlet Oxygen / Q000378:metabolism; D013452:Sulfonium Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D017319:Photosensitizing Agents; D013452:Sulfonium Compounds; D026082:Singlet Oxygen; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D010100:Oxygen
keywords: oxygen-independent photodynamic therapy; photoacid generator; silica nanoparticles; stimuli-responsive; sulfonium salt