Abstract 5420: Nano-engineered mesenchymal stem cells as targeted therapeutic carriers
Authors: Swayam Prabha, Tanmoy Sadhukha
Journal: Cancer Research (2014)

Abstract Poor availability of chemotherapeutics in deep-seated and metastatic cancers results in the development of drug resistance and failed therapeutic outcomes. Approaches that can specifically enhance drug delivery to the tumor tissue can potentially improve therapeutic efficacy while minimizing toxic side effects. In our current studies, we used nano-engineered mesenchymal stem cells (MSCs) as tumor-targeted therapeutic carriers. MSCs possess exquisite tumor homing capabilities. In addition, MSCs overexpress efflux transporters such as P-glycoprotein and are highly drug resistant. The inherent tumor-tropic and drug-resistant properties make MSCs ideal carriers for toxic payload. Since a majority of MSCs first accumulate in the lungs following systemic administration, this technology is particularly suitable for the delivery of anticancer therapeutics to lung tumors. The overall objective of this study was to investigate the efficacy of nano-engineered MSCs in non-small cell lung cancer. We hypothesized that incorporation of drug-loaded, polymeric nanoparticles in MSCs will allow for tumor-targeted and sustained drug delivery. Nanoparticles containing paclitaxel and imaging agent were formulated using poly (DL-lactide-co-glycolide) polymer by solvent evaporation technique and characterized for size, charge, drug loading and in vitro drug release. Nano-engineered MSCs were designed by loading MSCs with nanoparticles containing paclitaxel and an infrared (in vivo) or green fluorescent (in vitro) imaging agent and characterized for nanoparticle uptake using flow cytometry. Nano-engineered MSCs were characterized for in vitro cytotoxicity, differentiation potential and in vivo migratory potential. Human MSCs incubated with nanoparticles showed a steady increase in nanoparticle uptake, with saturation at 4 hours. Nanoparticles encapsulation did not affect the viability or the differentiation potential of MSCs. Nano-engineered MSCs resulted in dose-dependent cytotoxicity in A549 lung adenocarcinoma cells. An orthotopic lung tumor model was used to monitor the in vivo distribution of nano-engineered MSCs. Intravenous injection of A549 cells stably transfected with luciferase in mice resulted in formation of lung tumors that were monitored by bioluminescence imaging. Intravenous injection of nanoparticles alone resulted in non-specific biodistribution, with high accumulation in liver and spleen. Nano-engineered MSCs, in contrast, demonstrated selective accumulation and retention in lung tumors. These results indicate that nano-engineered MSCs can be loaded with high concentration of anticancer agents without affecting their migratory or drug resistance properties. Future studies will examine the anticancer efficacy of nano-engineered MSCs in an orthotopic mouse model of lung cancer. Citation Format: Swayam Prabha, Tanmoy Sadhukha. Nano-engineered mesenchymal stem cells as targeted therapeutic carriers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5420. doi:10.1158/1538-7445.AM2014-5420