Abstract 2790: Evaluation of S100A9 targeted nanoparticles containing rapamycin to treat pancreatic adenocarcinoma

Abstract

Abstract Despite Pancreatic cancer being expected to contribute to only 3% of new cancer cases in both males and females in 2019, it is expected to cause an estimated 45,750 deaths making it the third highest contributor to cancer deaths. This is due to the low survivability associated with pancreatic cancer which has a 5-year survival rate of only 9%. In order to address the poor prognosis common with pancreatic cancer, biomarkers are being used to create therapies targeted to specific cancer cells. The S100A8/A9 complex is a heterodimer, known for modulating the inflammatory response, and it is upregulated in a variety of cancers including pancreatic cancers. For this reason, we selected it as a targeting agent to deliver Rapamycin to pancreatic cancer cells via a mesoporous silica-encased gold nanorod (MS-GNR). The use of this nanoparticle allows an anticancer molecule to be encapsulated within the mesoporous silica matrix by further encapsulation of the nanoparticle with the pH sensitive polymer chitosan. A low pH tumor microenvironment induces relaxation of the chitosan surrounding this chitosan-capped mesoporous silica gold nanorod (CMG) allowing for the anticancer molecule to be released only in cancer cells. The gold nanorod at the core of this enables these nanoparticles to be imaged in real time via Multispectral Optoacoustic Tomography (MSOT). Using these tools, we linked S100A9 to a mesoporous silica-encased gold nanorod which contained Rapamycin held in via the chitosan polymer (S100A9-Rap-CMG). MSOT imaging revealed a strong uptake in S2013Q and MiaPaca pancreatic cancer cells. Further tests showed that at a pH 6.8 S100A9-Rap-CMG treatment resulted in an increase in cell death by 69% compared to treatment at physiologic pH of 7.4 by the S100A9-Rap-CMG's which did not induce cell death. This data indicates the feasibility of S100A9 as a targeting agent for pancreatic cancer cells and the potential benefits of nano-drug delivery of Rapamycin to treat pancreatic adenocarcinoma. The ultimate benefit of the nano-drug delivery includes both increased tumor targeting and mitigating premature drug release and offsite delivery. Citation Format: Karl Thomas, Molly McNally, Abhilash Samykutty, Lacey R. McNally. Evaluation of S100A9 targeted nanoparticles containing rapamycin to treat pancreatic adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2790.