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Updated: Mar 10, 2026
Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
Pegylated and nanoparticle-conjugated sulfonium salt photo triggers necrotic cell death
Alaa A Fadhel1, Xiling Yue1, Ebrahim H Ghazvini Zadeh1
1Department of Chemistry, University of Central Florida, Orlando, FL, USA.
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.
Insights
This study introduces a novel, oxygen-independent photodynamic therapy (PDT) agent using photoacid generators (PAGs) on silica nanoparticles (SiNPs). This approach effectively induces cancer cell death, even in oxygen-deprived environments, offering new therapeutic possibilities.
Area of Science:
- Biomedical Engineering
- Photochemistry
- Nanotechnology
Background:
- Photodynamic therapy (PDT) effectiveness is limited by tumor hypoxia.
- Singlet oxygen production, central to traditional PDT, is oxygen-dependent.
- Hypoxic tumors require alternative therapeutic strategies.
Purpose of the Study:
- To develop and test an oxygen-independent photoacid generator (PAG) as a novel PDT agent.
- To functionalize PAGs with silica nanoparticles (SiNPs) for enhanced delivery and control.
- To investigate the potential for treating hypoxic tumors with this new approach.
Main Methods:
- Developed polyethylene glycol (PEG)-functionalized and SiNP-enriched PAGs.
- Tested the PAGs' ability to induce necrotic cell death in HCT-116 cells.
- Investigated PAG delivery and compartmentalization within cells using SiNP conjugation (SiNP-PAG9).
Main Results:
- The developed SiNP-PAG9 effectively delivered the PAG into HCT-116 cells, localizing in lysosomes and endosomes.
- Upon light excitation, SiNP-PAG9 induced cell swelling and loss of adhesion, indicating cell death.
- The PAG system demonstrated oxygen-independent cytotoxicity.
Conclusions:
- The developed SiNP-PAG9 represents a promising oxygen-independent PDT agent.
- This approach can selectively induce cell death in hypoxic conditions, potentially in optically thick tissues.
- Further investigation into near-infrared two-photon absorption is warranted for deep tissue applications.
