Abstract 4394: Selective accumulation and specific tumor damage by folate receptor-targeted CA-4 prodrug as part of a combination of photodynamic therapy and site-specific chemotherapy

Abstract

Abstract A non-invasive or minimally invasive tumor ablation regimen is an attractive tool with which to control tumors. This approach is complementary to primary treatment options without causing systemic side effects or severe physical burdens from the treatment itself. Clinically approved photodynamic therapy (PDT) is one such regimen. In PDT, photosensitizers are activated by visible and near IR light to destroy tumors. However, the therapeutic efficacy of PDT is limited due to the spatial and temporal restrictions of the effector of PDT, singlet oxygen. We have been developing a new prodrug strategy that can overcome these limits by using a unique combination of PDT and site-specific chemotherapy. The prodrug is composed of photosensitizer and anticancer drug via a singlet oxygen-cleavable linker. Upon illumination, the prodrugs cause PDT damage and simultaneously release anticancer drugs only at the illuminated target area. In our previous publications, we reported 1) the design and synthesis of prodrugs of combretastatin A-4, 2) visible/ near IR light-controlled release of the drug from the prodrug, 3) bystander effects from the released anticancer drug, and 4) the superior antitumor effect of the prodrug compared to a simple combination of PDT and chemotherapy. Recently, a more advanced CA-4 prodrug was developed to achieve selective delivery to tumors via folate receptors (FRs) overexpressed in numerous cancer cell lines. The targeted prodrug showed FR-mediated uptake to FR-expressing cancer cells (colon 26 cells) in vitro and to FR-expressing tumors in vivo. Notably, the targeted CA-4 prodrug effectively ablated the tumors without causing collateral damage to the surrounding skin. Citation Format: Nkepang Gregory, Moses Bio, Pallavi Rajaptura, Samuel G. Awuah, Youngjae You. Selective accumulation and specific tumor damage by folate receptor-targeted CA-4 prodrug as part of a combination of photodynamic therapy and site-specific chemotherapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4394. doi:10.1158/1538-7445.AM2015-4394