This conference presentation was prepared for the Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXXI conference at SPIE BiOS, SPIE Photonics West 2023.
KEYWORDS: Breast cancer, Photodynamic therapy, Nanoparticles, In vitro testing, In vivo imaging, Mouse models, Therapeutic agents, Biomedical optics, Cancer, Safety
Multifunctional hybrid nanoparticles are being developed to carry a wide variety of therapeutic and imaging agents for multiple biomedical applications. Polysilsesquioxane (PSilQ) nanoparticles is a promising hybrid platform with numerous advantages to be used as delivery system for photodynamic therapy. In this work, we developed a redox-responsive PSilQ-based platform to transport and deliver simultaneously protoporphyrin IX (PpIX) and curcumin inside human cells. These PSilQ nanoparticles contain a high loading of PpIX (24.4 ± 2.5 %wt) and curcumin (7.6 ± 1.5 %wt), and are biodegraded inside cancer cells due to the high reducing environment. This multimodal delivery system shows a synergistic performance for the combined photo- and chemotherapy of the triple-negative breast cancer (TNBC) MDA-MB-231 cells. The safety and phototherapeutic efficacy of this PSilQ-based platform was evaluated in an orthotopic mice model of TNBC. The PSilQ nanoparticles are completely biodegraded and excreted from mice without any side effect. The efficacy data show that the PSilQ nanoparticles efficiently reduce tumor growth in the orthotopic mice model of TNBC. This work demonstrates that PSilQ nanoparticle-based platform is an excellent alternative for the combined photo- and chemotherapy of TNBC.
Photodynamic therapy (PDT) is a technique that combines light’s interaction with a photoactive substance to promote cellular death and that has been used to treat a wide range of maladies. Cancer is among the leading causes of death worldwide and has been a central issue assessed by PDT research and clinical trials over the last 35 years, but its efficiency has been hampered by photosensitizer buildup at treatment site. Nanotechnology has been addressing drug delivery problems by the development of distinct nanostructured platforms capable of increasing pharmacological properties of molecules. The association of nanotechnology’s potential to enhance photosensitizer delivery to target tissues with PDT’s oxidative damage to induce cell death has been rising as a prospect to optimize cancer treatment. In this study, we aim to verify and compare the efficiency of PDT using redox-responsive silica-based nanoparticles carrying protoporphyrin IX (PpIX) in vitro, in both tumor and healthy cells. Dose-response experiments revealed the higher susceptibility of murine melanoma cells (B16-F10 cell line) to PDT (630 nm, 50 J/cm2) when compared to human dermal fibroblasts (HDFn): after 24 h of incubation with 50 μg/mL nanoparticles solutions, approximately 80 % of B16- F10 cells were killed, while similar results were obtained in HDFn cultures when solutions over 150 μg/mL were used. Uptake and ROS generation assays suggest increased nanoparticle internalization in the tumor cell line, in comparison with the healthy cells, and greater ROS levels were observed in B16-F10 cells.
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