Synthesis of Carborane-Containing Porphyrin Derivatives for the Boron Neutron Capture Therapy of Tumors

The treatment of malignant brain tumors using conventional therapies and surgery often leads to tumor recurrence and/or unwanted side effects. Boron neutron capture therapy (BNCT) is a binary and localized form of treatment for brain tumors and other difficult-to-treat cancers that uses nontoxic boron-containing agents. Boronated porphyrins and derivatives constitute a class of highly promising third-generation boron delivery agents for BNCT. These stable, tumor-specific, and fluorescent macrocycles can be synthesized with high boron content, can deliver therapeutic amounts of boron to target sites, and allow tumor detection and treatment planning by optical imaging. In addition, boronated porphyrins have shown low toxicity and enhanced tumor selectivity and retention times comparedwith clinically approved BNCT agents, BSH and BPA. In this article the synthesis of carboranylcontaining porphyrins and derivatives for application in BNCT is reviewed, with special emphasis on macrocycles reported in the last decade. Current strategies for enhancing the biological efficacy of BNCT agents involve their association with tumor-targeting molecules, such as polyamines and peptides, for improved tumor selectivity and accumulation.