Targeting Ovarian Cancer with Porphysome Nanotechnology
Technical Report,30 Sep 2013,29 Sep 2014
University Health Network Toronto Canada
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Current conventional therapy includes surgery and chemotherapy has limitation for ovarian cancer OC management. OC remains the most lethal gynecologic malignancy and requires a novel therapeutics development to effectively change the current paradigm of care. Porphysomes with intrinsic multimodal biophotonic properties, favorable in vivo behaviors, and low toxicity, provide a multimodal imaging and therapeutic platform for OC management. In this project, we have developed a folate receptor FR targeted porphysome for potentially targeted OC management as FR expression has been reported in up to 90-95 of epithelial OC. We have demonstrated FR-mediated cell uptake of nanoparticles. After systematic administration to FR-positive tumor-bearing mice, the Cu-64 labeled FR-porphysome were capable to detect the tumor by PET imaging and NIR fluorescence imaging. In addition, FR-mediated delivery triggered nanostructure rapid disruption that ultimately restored the photodynamic reactivity of monomeric porphyrins which was quenched in the intact nanostructure, thus enabling selective and potent photodynamic therapy PDT. To further improve the pharmacokinetics of FR-porphysome, we developed ultra-small porphyrin nanovehicle PLP with great biocompatibility, favorable pharmacokinetics, intrinsic multi-imaging modalities, potent PDT, and stable drug delivery functionalities. Therefore, PLPs provide a multimodal imaging and therapeutic platform that could enhance OC diagnosis by integrating PETCT and fluorescence imaging, and improve OC therapeutic efficacy and specificity by tailoring treatment via fluorescence-guided surgical along with selective PDT, and potential chemotherapy. For Year 2, we plan to focus our efforts on the GMP-kit development for 64Cu-porphysome to meet the Health CanadaFDA regulation for CTA filing, which will then be ready for the companion project PI A Oza for Phase I clinical trials.
- Medicine and Medical Research