Abstract 5073: A novel in-situ nanoparticle self-assembly for combination delivery of therapeutics to non-small cell lung cancer

Abstract

Abstract Background: Lung cancer is a predominant cause of morbidity and mortality across the world. Among all types of cancers, lung cancer is the leading cause of cancer mortalities in the United States. Non-small cell lung cancer is one of the dominant divisions of lung cancer that solely represents 85-90% of all lung cancer cases. Up to the present time, primary treatment regimens for this cancer include radiation therapy, chemotherapy, and surgery, with chemotherapy being the best option thus far. Despite the eminent benefits of chemotherapy, its value is offset by severe side effects such as renal and/or hepatic toxicity or insufficient amounts of drug available at the target site. Such pitfalls can be handled by employing natural compounds (polyphenols, phytochemicals, xanthonoid, etc.,) as chemopreventives or chemosensitizers which can improve chemotherapy activity while reducing its systemic side effects and drug resistance. To this end, our recent efforts demonstrated a synergistic therapeutic benefit of gambogic acid (GA) and gemcitabine (Gem) against lung cancer. However, simultaneous delivery of these two drugs at the tumor site is highly challenging. Therefore, development of an injectable nanoformulation that can effectively deliver both hydrophobic (GA) and hydrophilic (Gem) drugs in one formulation is a clinically unmet need. Methods: Pursuing the novel nanotherapy approach, our lab has developed an in-situ biodegradable and biocompatible human serum albumin (HSA) and tannic acid (TA) mediated complexed GA and Gem nanoparticles (G-G@HTA NPs) using the solvent evaporation method. G-G@HTA NPs formation was confirmed by particle size, FT-IR, and H-NMR. A superior therapeutic activity of G-G@HTA NPs was demonstrated by multiple in vitro functional assays as well as in an animal mouse model. Results: Our results confirmed that G-G@HTA NPs have the ideal particle size and surface charge for cancer cell/tissue delivery which can clearly be evident by preferential uptake of these nanoparticles in lung cancer cells. Further, G-G@HTA NPs superiorly inhibited cell proliferation and clonogenicity of NSCLC cells. Additionally, G-G@HTA NPs revealed an obvious and precise targeting of tumors in vivo. The promoted and more synergistic anti-tumor efficacy of G-G@HTA NPs was attained than that of combined treatments and single drugs treatments. These events were resulted with no apparent systemic and organ toxicities. Conclusion: In summary, this study details the design of a novel nanocarrier and provides an optimized strategy for constructing dual-loaded nanoparticles using a biodegradable, non-toxic, human serum albumin-tannic acid-based platform for GA and Gem co-delivery in the treatment of NSCLC which confirms a strong feasibility to implement such synergistic nanomedicine regimen in pre-clinical and clinical translations in future. Citation Format: Elham Hatami, Prashanth K. Nagesh, Neeraj Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu. A novel in-situ nanoparticle self-assembly for combination delivery of therapeutics to non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5073.