Mesenchymal stem cell derived extracellular vesicles loaded with at least one photosensitizer and uses thereof for the treatment of peritoneal carcinomatosis

Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity. The occurrence of peritoneal carcinomatosis (PC) has been shown to significantly decrease overall survival in patients. Treatment of residual microscopic disease remains a challenge with new anticancer modalities development. Now, the inventors propose an innovative therapeutic management of peritoneal carcinomatosis (PC) that is bio-inspired and tumor-targeted by engineering MSC-derived EVs to encapsulate a photosensitizer (mTHPC) for improved photodynamic therapy efficiency and safety. In this work, the inventors first evaluated the biodistribution of EVs-mTHPC in a murine PC model and highlighted superior accumulation of mTHPC in the tumor compared to other mTHPC formulations (free drug and liposomal one (Foslip®). The effectiveness of PDT mediated by mTHPC vectorized in EVs has then been evaluated in PC. In accordance with pharmacokinetics, the results revealed both an enhanced light-induced therapeutic efficiency in terms of tumoral cytotoxicity, safety for surrounding tissue after laser irradiation, immunomodulation and improved survival time. Thus, the present invention relates to mesenchymal stem cell derived extracellular vesicles loaded with at least one photosensitizer and uses thereof for the treatment of peritoneal carcinomatosis.

Keywords: Oncology, photodynamic therapy, MSC, peritonealrncarcinomatosis, pleural metastasis
Patent Application number: European Procedure (Patents) (EPA) - 21 Nov. 2019 - 19 306 495.3
Inventors:
POCARD MarcPIFFOUX MaxMARANGON IrisWILHEM ClaireGAZEAU FlorencePINTO AmandineSILVA (BRUN-GRAEPPI) Amanda K. Andriola
Publications:
Amandine Pinto et al. ACS Nano 2021 15 2 3251–3263

Reference:

BIO19434-T1

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