Abstract Purpose of the study: The dietary compound Capsaicin is the hot and pungent ingredient of chili peppers. Preliminary data in our laboratory have found that capsaicin displays robust growth-inhibitory activity in human lung cancers. However, the clinical applications of capsaicin as a viable anti-cancer drug are hindered by its adverse side effects, such as gastric irritation, nausea, stomach cramps and a burning sensation in the gut. Clinical trials which explored the pain-relieving activity of capsaicin found that patients who orally ingested capsaicin discontinued taking the drug due to its unpleasant side effects. One strategy to circumvent this drawback is to encapsulate capsaicin in long-acting formulations (like polymeric nanoparticles). Once capsaicin is entrapped in these polymeric nanoparticles, it is released at a very slow rate, so it does not produce any “heat-sensation” and adverse side effects in patients Experimental procedures: Capsaicin poly(lactic-co-glycolic acid) nanoparticles (hereby called CAP-PLGA-NPs] were custom synthesized by a biotech company. The physicochemical properties of these nanoparticles were provided by the vendor. We tested the pro-apoptotic activity of these CAP-PLGA-NPs in a panel of human NSCLC cell lines. We also measured the impact of these CAP-PLGA-NPs on the growth of normal human lung, liver and kidney cells. We also performed soft agar assays to evaluate the ability of CAP-PLGA-NP to inhibit anchorage independent-growth on soft agar. Finally, we tested the anti-neoplastic activity of CAP-PLGA-NPs in SCID mice xenografted with human NSCLC tumors. Results: The CAP-PLGA-NP displayed greater pro-apoptotic activity than capsaicin in human NSCLCs. CAP-PLGA-NP inhibited colony-formation in soft agar assays. Most interestingly, CAP-PLGA-NP did not impact the growth of normal human lung, liver and kidney cells. The intravenous administration of CAP-PLGA-NPs decreased the rate of human NSCLC tumors xenografted in SCID mice Conclusions: The long-acting capsaicin drug formulation, namely CAP-PLGA-NP, may be a promising nutrition-based drug in human NSCLCs. Support or Funding Information Funding for our study was supported by the NIH R15-AREA Grant (2R15CA161491-02 and 2R15CA161491-03), the Women's Health T3: 3P20GM103434-23W1 (PI: Dr. G Rankin) to PD and MAV and the NIAID-AI151970 grant to TEL. This study was supported in part by the West Virginia IDeA Network of Biomedical Research Excellence (WV-INBRE) grant (NIH grant P20GM103434; PI: Dr. G. Rankin), the National Institute of General Medical Sciences of the National Institutes of Health under the award number P30GM122733. Citation Format: Kushal Jignesh Modi, Reagan S. Light, Kaitlyn B. Conley, Sarah L. Miles, Piyali Dasgupta. Capsaicin nanoparticles display robust growth-inhibitory activity in human NSCLC abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3023.
Modi et al. (2026) studied this question.