Abstract 477: Tumor treating fields (TTFields) targeted self assembling nanoparticles for pancreatic cancer treatment: In vitro and in vivo assessment

Abstract

Abstract Tumor Treating Fields (TTFields) is a novel, non-invasive and safe treatment modality, which is prescribed to be used in conjunction with classical anticancer chemotherapeutic drugs. TTFields when used alone are safe, but their use in combination with classical chemotherapy continues to offer drug related adverse reactions which ultimately impacts the patient compliance. To address this challenge, we earlier reported meticulously optimized self-assembling cationic-anionic polymer nanoparticles (S-CAP NPs) with average particle size of about 200 nM, encapsulation efficiency of 55-65 % and sustained drug release over 60 h. We also reported that, TTFields were capable of destabilizing the S-CAP NPs leading to targeted drug release. The results were also corroborated with in vitro cytotoxicity and colony formation studies in presence of TTFields using multiple pancreatic cancer cell lines. After establishing the proof-of-concept, the objective was to assess the in vitro cellular uptake of S-CAP NPs. For this, fluorescent dye loaded S-CAP NPs were developed and subjected to cellular uptake analysis. The in vitro cellular uptake studies confirmed the enhanced uptake of S-Cap NPs by passive diffusion in the pancreatic cancer cell lines compared to normal pancreatic epithelial cell line. The studies corroborated preferential cellular uptake of S-Cap NPs by the pancreatic tumor. Among all the formulations, the chitosan- bovine serum albumin S-CAP NPs was most optimum and was used for in vivo safety studies. For this, in vivo acute and repeated dose 28-day toxicity of the optimum placebo S-CAP NPs was conducted in Sprague Dawley rats (Western University of Health Sciences Protocol #R20IACUC031) and OECD guidelines. The in vivo studies showed a LD50 value above 2000 mg/kg and NOAEL value of 1000 mg/kg. These high doses safety of S-CAP NPs confirmed the potential of this approach for future preclinical efficacy studies followed by clinical translation. Lastly, the in vitro stability studies were conducted as per the ICH guidelines for a period of 36 months and the formulations were concluded to be stable. The tumor targeting potential, in vivo safety and stability of S-CAP NPs, establish their translational potential for TTFields triggered targeted drug release in cancer treatment. This approach will not only reduce the adverse effect associated with combination of TTFields and chemotherapy but can also be explored as a platform technology for management of other cancers. This study is supported by AACR-Novocure tumor treating fields research fellowship. Citation Format: Preshita Prafulla Desai, Sunil Prabhu. Tumor treating fields (TTFields) targeted self assembling nanoparticles for pancreatic cancer treatment: In vitro and in vivo assessment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 477.