A desired goal of targeted cancer treatments is to achieve high tumor specificity with minimal side effects.
Despite recent advances, this remains difficult to achieve in practice as most approaches rely on biomarkers or physiological differences between malignant and healthy tissue, and thus benefit only a subset of patients in need of treatment. To address this unmet need, we introduced a Click Activated Protodrugs Against Cancer (CAPAC) platform that enables targeted activation of drugs at a specific site in the body, i.e., a tumor. In vitro evaluation of cytotoxicity, solubility, stability and activation rendered the protodrug of doxorubicin, SQP33, as the most promising candidate for in vivo studies.
Studies in rodents show that a single injection of the tetrazine-modified biopolymer, SQL70, efficiently captures SQP33 protodrug doses given at 10.8-times the maximum tolerated dose of conventional doxorubicin with greatly reduced systemic toxicity.
