Abstract 1862: Biomimetic poly lactic acid based nanoparticles for tumor targeted delivery of chemotherapeutic drugs

Abstract Global cancer burden is increasing day by day and to mitigate this situation, chemotherapy is widely used as systemic treatment modality. Along with many pros, chemotherapy does have various cons such as: systemic toxicity, faster degradation in physiological conditions hence low bioavailability and poor tumor accumulation. To overcome these shortcomings, nano-drug delivery systems are used. The nanoparticles can be tailor made according to physiological conditions of the tumor microenvironment. Herein, the redox responsive polymer has been synthesized by introducing the disulphide linkage in the polymer. The chemo-drug Pirarubicin has been encapsulated by double emulsion method in the nanoparticles prepared with redox-responsive polymer. The drug release profile indicated the release of the drug is more efficient in presence of 10mM Dithiothreitol (reducing agent for disulphide linkage) when compared to 0mM dithiothreitol, hence suggesting the successful synthesis of stimulus responsive drug delivery system. In this context, this study investigates the therapeutic efficacy of Pirarubicin encapsulated in polylactic acid based redox responsive nanoparticle(NP) whose surface have been modified with tumor and macrophage cell membranes. The coated cell membrane provides advantages such as immune escape, long blood circulation time, specific molecular recognition and tumor cell targeting. The prepared nanoparticles have a hydrodynamic size in nano-range with high negative zeta potential. The cellular internalization studies of free drug vs the cell membrane coated NPs (CMNPs) were done and it was confirmed with fluorescence microscopy as well as flow cytometry that CMNPs were internalized more efficiently in one hour drug incubation study. The same was confirmed when cancer cell proliferation inhibition assay was done, and half maximal inhibitory concentration was highest in case of uncoated NP, then that of free a drug, and lowest in case of CMNPs. This study provides the synthesis and characterization of redox responsive polymer, preparation of cell membrane coated nanoparticles and in-vitro studies for the same. This study has a future scope in the field of personalized medicine at much cheaper price when compared to active targeting methods by antibodies, CART, proteins etc. Citation Format: Harshdeep Kaur, Harpal Singh. Biomimetic poly lactic acid based nanoparticles for tumor targeted delivery of chemotherapeutic drugs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1862.