Targeting Ovarian Cancer with Porphysome Nanotechnology
Technical Report,30 Sep 2015,29 Sep 2016
University Health Network Toronto Canada
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Purpose The Porphysome is a first-in-class porphyrin-based nanotheransotic with inherent biophotonic, photo-physical, and metal chelation properties that can be exploited for multi-modal imaging in Vivo. Herein we report preliminary preclinical data of the use of systemically administered non-targeted Porphysomes for the detection of orthotopic ovarian lesions. Methods Two ovarian tumour xenograft models are established with human SK-OV-3 and OV-90 cell lines installed into one ovary orthotopic of athymic NuNu mice. Upon reaching 3.5 mm tumour size, mice are administered non-targeted Porphysome nanovesicles intravenous, bolus, 10 mg kg-1 porphyrin dose. Mice are divided into two treatment groups receiving either unlabelled Porphysomes or positron-emitting Copper-64 64Cu-labelled Porphysomes 64Cu-Porphysomes. Sham surgical controls and vehicle controls are included. 24-hours post-injection the mice receiving Porphysomes are sacrificed and tissue biodistribution performed using ex Vivo tissue homogenate fluorescence. The mice receiving 64Cu-Porphysomes are sacrificed and tissue biodistribution performed using ex Vivo tissue gamma -counting. Results Quantification of 64Cu signal -counting revealed insignificant differences in the accumulation of non-targeted 64Cu-Porphysomes in ovarian lesions versus healthy ovaries. Quantification of porphyrin fluorescence tissue homogenate fluorescence also revealed insignificant differences in Porphysome accumulation. Taken together, these preliminary data suggest that non-targeted Porphysomes relying solely on passive mechanisms for accumulation e.g., enhanced permeability and retention EPR-effect phenomena is an inadequate strategy for yielding significant accumulation and retention of Porphysomes in malignant ovarian tissues compared with healthy ovarian tissues.
- Medicine and Medical Research