Abstract 4502: Aptamer conjugated prostate specific membrane antigen (PSMA) targeting nanobees for prostate cancer prevention and therapy

Abstract

Abstract Melittin (MEL), a major peptide component of bee venom (BV), has shown chemopreventive as well as chemotherapeutic effects against many cancers in preclinical model systems. However, its applicability to humans has met with limited success due to several issues including its toxicity, nonspecificity, degradation, inefficient systemic delivery and limited bioavailability. Earlier, the concept of "nanochemoprevention" i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention is introduced. Then, "non-targeted nanobees" i.e. nanoformulated mellitin is developed to exhibit excellent anti-prostate cancer efficacy in vitro and in animal models coining the concept as ‘Nanobee- Chemoprevention’. Here, we are extending this work and developed nanobees targeted with small molecular entities (A10 2′-fluoropyrimidine RNA aptamers (Apt)), able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa) and evaluated their efficacy in preclinical studies. The Apt-Nanobees led to an enhanced anti-proliferative activity in PCa cell lines compared to the free melittin. The behavior of Apt-Nanobees in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor using nanobees with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of targeted nanobees enhanced the bioavailability and limited unwanted toxicity of melittin, thus leading to a significant potential for probable clinical outcome. Citation Format: Islam Rady, Sayed Bakry, Fatma Abou El-Azm, Hasan Mukhtar. Aptamer conjugated prostate specific membrane antigen (PSMA) targeting nanobees for prostate cancer prevention and therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4502.