Dual‐Targeted Lipid Nanotherapeutic Boost for Chemo‐Immunotherapy of Cancer

• DOI: 10.1002/adma.202106350
• Publication Date: 2022-01-19T13:31:22Z
• Authors: Seok‐Beom Yong; Srinivas Ramishetti; Meir Goldsmith; Yael Diesendruck; Inbal Hazan‐Halevy; Sushmita Chatterjee; Gonna Somu Naidu; Assaf Ezra; Dan Peer
• Keywords: Cancer Immunotherapy; Reprogramming

Chemo-immunotherapy is a combination of "standard-of-care" chemotherapy with immunotherapy and it considered the most advanced therapeutic modality for various types cancers. However, many cancer patients still poorly respond to current regimen chemo-immunotherapy suggest nanotherapeutics as boosting agent. Recently, heme oxygenase-1 (HO1) shown act an immunotherapeutic molecule in tumor myeloid cells, addition general chemoresistance function cells suggesting that HO1-targeted therapeutics can become novel, optimal strategy clinic. Currently available HO1-inhibitors demonstrate serious adverse effects clinical use. Herein, cell- cell-dual targeted HO1-inhibiting lipid nanotherapeutic boost (T-iLNTB) developed using RNAi-loaded nanoparticles. T-iLNTB-mediated HO1-inhibition sensitizes chemotherapeutics by increasing immunogenic cell death, directly reprograms distinguished phenotype. Furthermore, reprogramming T-iLNTB induces CD8+ cytotoxic T recruitment, which drives "Cold-to-Hot" transition correlates improved responsiveness immune checkpoint inhibitor therapy. Finally, ex vivo study proves affects macrophage differentiation. This demonstrates potential novel chemo-immunotherapy.