Traditional external light-based Photodynamic Therapy (PDT)’s application is limited to the surface and minimal thickness tumors because of the inefficiency of light in penetrating deep-seated tumors. To address this, the emerging field of radiation-activated PDT (radioPDT) uses X-rays to trigger photosensitizer-containing nanoparticles (NPs). A key consideration in radioPDT is the energy transfer efficiency from X-rays to the photosensitizer for ultimately generating the phototoxic reactive oxygen species (ROS). In this study, we developed a new variant of pegylated poly-lactic-co-glycolic (PEG-PLGA) encapsulated nanoscintillators (NSCs) along with a new, highly efficient ruthenium-based photosensitizer (Ru/radioPDT). Characterization of this NP via transmission electron microscopy, dynamic light scattering, UV-Vis spectroscopy, and inductively coupled plasma mass-spectroscopy showed an NP size of 120 nm, polydispersity index (PDI) of less than 0.25, high NSCs loading efficiency over 90% and in vitro accumulation within the cytosolic structure of endoplasmic reticulum and lysosome. The therapeutic efficacy of Ru/radioPDT was determined using PC3 cell viability and clonogenic assays. Ru/radioPDT exhibited minimal cell toxicity until activated by radiation to induce significant cancer cell kill over radiation alone. Compared to protoporphyrin IX-mediated radioPDT (PPIX/radioPDT), Ru/radioPDT showed higher capacity for singlet oxygen generation, maintaining a comparable cytotoxic effect on PC3 cells.
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Light-Activated Protoporphyrin IX-Based Polysilsesquioxane Nanoparticles Induce Ferroptosis in Melanoma Cells
The use of nanoparticle-based materials to improve the efficacy of photodynamic therapy (PDT) to treat cancer has been a burgeoning field of research in recent years. Polysilsesquioxane (PSilQ) nanoparticles with remarkable features, such as high loading of photosensitizers, biodegradability, surface tunability, and biocompatibility, have been used for the treatment of cancer in vitro and in vivo using PDT. The PSilQ platform typically shows an enhanced PDT performance following a cell death mechanism similar to the parent photosensitizer. Ferroptosis is a new cell death mechanism recently associated with PDT that has not been investigated using PSilQ nanoparticles. Herein, we synthesized a protoporphyrin IX (PpIX)-based PSilQ platform (PpIX-PSilQ NPs) to study the cell death pathways, with special focus on ferroptosis, during PDT in vitro. Our data obtained from different assays that analyzed Annexin V binding, glutathione peroxidase activity, and lipid peroxidation demonstrate that the cell death in PDT using PpIX-PSilQ NPs is regulated by apoptosis and ferroptosis. These results can provide alternative approaches in designing PDT strategies to enhance therapeutic response in conditions stymied by apoptosis resistance.
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- Award ID(s):
- 1835688
- NSF-PAR ID:
- 10311871
- Date Published:
- Journal Name:
- Nanomaterials
- Volume:
- 11
- Issue:
- 9
- ISSN:
- 2079-4991
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/nano11092324
