LAUSR

The identification of therapeutic nanoparticles formulation with preferential distribution to the tumor microenvironment remains an unsolved challenge. We have developed a high-throughput synthesis and screening platform to discover novel tumor-targeting liposomal nanoparticles. Over 1,000 unique liposomal formulations were synthesized using a combinatorial approach. The characterization of physicochemical properties (e.g., size, charge and stability) allowed the prioritization of ~500 formulations further profiled with in vitro cell-based assays (e.g., cell binding, cytotoxicity and cell barrier crossing). A subset of formulations with diverse properties was selected to create a library of 47 DNA-barcoded nanoparticles. The pharmacokinetics and biodistribution of the formulations library were measured in tumor xenografts mouse models in a highly multiplexed fashion by sequencing the DNA barcodes. The established synthesis and screening platform provides an effective approach to identify novel liposomal formulations with improved tumor and tissue distribution profile. Note: This abstract was not presented at the conference. Citation Format: Mark Audeh, Manali Dwarakanath, Michael Hopkins, Alisha Knudson, Sally Kwok, Stephen Morton, Nikki Peck, Tim Ruckh, Sarah Sanowar, Zach Scott, Peter Thana, Gary Tong, Aaron Topol, Alberto C Vitari, Eugeni Vaisberg, Jane Wang, Stanley Wong. High-throughput synthesis and screening for tumor-targeting liposomal nanoparticles [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B66.