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.

Engineering Intrinsically Zirconium-89 Radiolabeled Self-Destructing Mesoporous Silica Nanostructures for In Vivo Biodistribution and Tumor Targeting Studies.

A systematic study of in vitro and in vivo behavior of biodegradable mesoporous silica nanoparticles (bMSNs), designed to carry multiple cargos (both small and macromolecular drugs) and subsequently self-destruct following release of their payloads, is presented. Complete degradation of bMSNs is seen within 21 d of incubation in simulated body fluid. The as-synthesized bMSNs are intrinsically radiolabeled with oxophilic zirconium-89 (89Zr, t1/2 = 78.4 h) radionuclide to track their in vivo pharmacokinetics via positron emission tomography imaging. Rapid and persistent CD105 specific tumor vasculature targeting is successfully demonstrated in murine model of metastatic breast cancer by using TRC105 (an anti-CD105 antibody)-conjugated bMSNs. This study serves to illustrate a simple, versatile, and readily tunable approach to potentially overcome the current challenges facing nanomedicine and further the goals of personalized nanotheranostics.