Tumor Treating Fields (TTFields) have been clinically proven as safe, effective, and non-invasive approach for cancer treatment. Specifically, TTFields in conjunction with Gemcitabine/nab-Paclitaxel have shown promising results in Phase II pancreatic cancer (PC) PANOVA study. It is imperative to understand here that while TTFields are very safe, concurrent use of anticancer drugs will continue to elicit non-site-specific adverse effects resulting in overall low patient compliance. To overcome this drawback, we have developed an innovative strategy called ‘Tumor Treating Fields Triggered Targeting of Nanoparticles in Cancer (TTFields-TTONIC)'. For this, self-assembling cationic-anionic polymer nanoparticles (S-CAP NPs) encapsulating Gemcitabine as a model anticancer drug were developed. The hypothesis involves combination of NPs and TTFields wherein the developed NPs will be preferentially taken up by the tumor owing to leaky vasculature. Further, only under the applied TTFields, the NPs will be destabilized due to high charge density of cationic and anionic polymers leading to targeted release of encapsulated drug at the tumor site (reduction in non-site-specific side effects). For this, multiple batches of two types of S-CAP NPs [chitosan- bovine serum albumin (Chitosan-BSA) and polyethylenimine- bovine serum albumin (PEI-BSA)] were developed. The formulations were optimized using mathematical modelling and Design Expert® software to achieve low particle size and optimum encapsulation efficiency. Based on the results, 2 formulations from each type i.e., chitosan- BSA S-CAP NPs [Batch C4 - particle size: 210.54 ± 38.96 nm, PDI: 0.194, encapsulation efficiency: 61.26 ± 5.11%, zeta potential: (+) 7.38 ± 3.11; Batch C7 - particle size: 215.67 ± 32.55 nm, PDI: 0.201, encapsulation efficiency: 65.31 ± 5.84 %, zeta potential: (+) 3.22 ± 1.28] and PEI-BSA S-CAP NPs [Batch P5 - particle size: 198.29 ± 41.05 nm, PDI: 0.227, encapsulation efficiency: 58.83 ± 3.33%, zeta potential: (+) 8.17 ± 2.63; Batch P8 - particle size: 209.92 ± 31.33 nm, PDI: 0.196, encapsulation efficiency: 64.31 ± 5.13%, zeta potential: (+) 11.49 ± 2.99] were shortlisted that exhibited particle size ~ 200 nm and encapsulation efficiency in range of 55-65 %. All the formulations exhibited sustained drug release profile over a period of 60 h wherein chitosan- BSA S-CAP NPs showed slower drug release compared to PEI-BSA S-CAP NPs (P<0.05). All formulations were subjected to stability studies as per the ICH guidelines wherein the formulations were observed to be stable. Further, the conventional MTS inhibitory assay and colony formation assay against the PC cell lines (Panc-1 and Mia Paca-2) showed significant efficacy with the PEI-BSA S-CAP NPs (P<0.01) compared to chitosan-BSA S-CAP NPs. In the next phase, efficacy of S-CAP NPs against the PC cell lines in presence of TTFields will be analyzed followed by in vivo safety studies. The success of this strategy will not only enhance the safety of combination treatment involving TTFields-anticancer drugs but will also establish a newer application of TTFields as a targeting modality. The work is funded by AACR-Novocure tumor treating fields research fellowship (2019-2021).
Citation Format: Preshita Prafulla Desai, Sunil Prabhu. Drug loaded nanoparticle targeting of pancreatic cancer using tumor treating fields (TTFields) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB023.