Development of a high payload, cancer-targeting liposomes of methyl aminolevulinate for intraoperative photodynamic diagnosis/therapy of peritoneal carcinomatosis

Methyl aminolevulinate (MAL) is a photosensitizer topically used for photodynamic diagnosis (PDD) and photodynamic therapy (PDT) of skin pre-cancers and cancers. In this study, our goal is to expand the application of MAL to dual intraoperative PDD and PDT of peritoneal carcinomatosis. A new liposomal MAL formulation (lipMAL) designed for systemic or intraperitoneal administration was developed. LipMALs prepared by ammonium sulfate gradient technique achieved MAL payload up to 18% (w/w) with drug encapsulation efficiency in the range of 15.1-31.5%. All lipMALs demonstrated controlled MAL release behavior, and achieved strong fluorescence in cancer cells (SKOV3) but minimal fluorescence in non-cancer peritoneal cells (B14FAF28-G3). LipMALs led to significantly higher fluorescence levels than free MAL groups (P < 0.05), up to 6.8-fold of the free MAL fluorescence levels in SKOV3 cells. The PDD performance of lipMALs was also compared with free MAL in SKOV3/ B14FAF28-G3 co-cultures simulating ovarian cancer micrometastases on peritoneal surface. The lipMAL-treated cancer colonies glew more brightly than the free MAL treated colonies and were clearly distinguishable from the dim peritoneum background with unaided eyes. LipMAL also achieved significantly stronger anticancer PDT effects than free MAL both in terms of cell viability and colony-formation (P < 0.05) while demonstrating minimal dark toxicity. To conclude, a new promising aid for the surgeons to achieve more complete resection of tumors and PC micrometastases and clean up any residual cancer cells undetected was developed.

Automated summary

A new liposomal MAL formulation (lipMAL) designed for systemic or intraperitoneal administration was developed in this study to expand the application of MAL to dual intraoperative PDD and PDT of peritoneal carcinomatosis. LipMALs demonstrated controlled MAL release behavior, achieved strong fluorescence in cancer cells, and led to significantly higher fluorescence levels than free MAL groups, showing promising anticancer PDT effects.