Abstract 992: Comparative analyses of drug-loaded exosomal preparations from different cell types reveal distinctive loading capability, yield, and anti-tumor efficacies

Abstract

Abstract Cancer remains one of the leading causes of death worldwide regardless of technological advancements. Inefficiency of current drug-delivery regimes is one of the important factors that limits the therapeutic efficacy of existing chemotherapeutics thus contributing to cancer mortality. To address this limitation, synthetic nanotechnology-based delivery systems have been developed; however, they raise concern of inducing adverse immunogenic reactions. Exosomes are non-immunogenic nano-sized vesicles that have received significant attention as efficient drug delivery system. Here we evaluated the efficacy of different cell types viz. pancreatic cancer cells (PCCs), pancreatic stellate cells (PSCs) and macrophages (MØs) for drug packaging and release into exosomes. PCCs shed the most exosomes and were the most efficient in drug loading followed by MØs and PSCs as examined by HPLC quantification. However, when compared for anti-tumor efficacy, MØs-derived exosomes-loaded with DOX (MØ-Exo-DOX) showed highest activity followed by PSCs and PCCs in WST-1 and Annexin V staining assays. These varying anti-tumor activities likely resulted from non-drug contents of exosomes since we did not observe any significant differences in their uptake by the cancer cells. Altogether, our data suggest that donor cell-specific differences exist in exosomes, which could influence their utility as drug carrier for therapeutic purposes. Citation Format: RAJASHEKHAR KANCHANAPALLY, Sachin Kumar Deshmukh, Suhash Reddy Chavva, Nikhil Tyagi, Sanjeev Kumar Srivastava, Girijesh Kumar Patel, Ajay P. Singh, Seema Singh. Comparative analyses of drug-loaded exosomal preparations from different cell types reveal distinctive loading capability, yield, and anti-tumor efficacies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 992.