Abstract B060: Enhanced therapeutic efficacy of a bioflavonoid loaded lipid nanoparticles via remodeling tumor microenvironment (TME) and KEAP1-NRF2 signaling in a murine breast tumor model

Abstract Investigations on bioactive phytoconstituents, especially bioflavonoids and their role in the mitigation of breast cancer have directed our interest to 2-(3,4-Dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one or taxifolin (TX) which possesses potent chemotherapeutic potential in murine breast cancer model. However, it has been observed to possess poor aqueous solubility and thus truncated bioavailability which limit its pharmacological efficacy. The current study focuses on engineering a stable lipid nano-cargo with sufficient entrapment efficiency for hydrophobic TX to produce significantly improved anti-breast cancer activity. The TX-nanoliposomes were exhaustively characterized through various physico-chemical parameters (hydrodynamic particle size and zeta potential, FT-IR, XRD, TGA, DSC, FESEM etc.) and subjected to various in vitro, in vivo and molecular biology studies for efficacy. While the nano-cargo formulation showed enhanced cytotoxicity than raw bioflavonoid against breast cancer, its cytocompatibility as well as hemocompatibility evinced further preclinical investigations. This non-leaky, lipid nano-shuttle, owing to its optimal release kinetics and passive targeted delivery of TX augmented the chemotherapeutic potential against breast cancer through modulating the tumor microenvironment (TME) with infiltration of dominant CD3+/CD8+T-cells along with iNOS+M1-macrophages and Keap1-Nrf2 antioxidant signaling (within the cells). The current study proves that TX-nano cargo enhanced the chemotherapeutic efficacy against breast cancer by improving bioavailability and targeting delivery, leading to TME-remodeling. Citation Format: Priyashree Sunita, Rosa Sahu, Shakti P Pattanayak. Enhanced therapeutic efficacy of a bioflavonoid loaded lipid nanoparticles via remodeling tumor microenvironment (TME) and KEAP1-NRF2 signaling in a murine breast tumor model [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B060.