Tumor-Tropic Adipose-Derived Mesenchymal Stromal Cell Mediated Bi2 Se3 Nano-Radiosensitizers Delivery for Targeted Radiotherapy of Non-Small Cell Lung Cancer

Abstract

With the successful marriage between nanotechnology and oncology, various high-Z element containing nanoparticles (NPs) are approved as radiosensitizers to overcome radiation resistance for enhanced radiotherapy (RT). Unfortunately, NPs themselves lack specificity to tumors. Due to the inherent tropism nature of malignant cells, mesenchymal stem cells (MSCs) emerge as cell-mediated delivery vehicles for functional NPs to improve their therapeutic index. Herein, radiosensitive bismuth selenide (Bi₂ Se₃ ) NPs-laden adipose-derived mesenchymal stromal cells (AD-MSCs/Bi₂ Se₃ ) are engineered for targeted RT of non-small cell lung cancer (NSCLC). The results reveal that the optimized intracellular loading strategy hardly affects cell viability, specific surface markers, or migration capability of AD-MSCs, and Bi₂ Se₃ NPs can be efficiently transported from AD-MSCs to tumor cells. In vivo biodistribution test shows that the Bi₂ Se₃ NPs accumulation in tumor is increased 20 times via AD-MSCs-mediated delivery. Therefore, AD-MSCs/Bi₂ Se₃ administration synchronized with X-ray irradiation controls the tumor progress well in orthotopic A549 tumor bearing mice. Considering that MSCs migrate better to irradiated tumor cells in comparison to nonirradiated ones and MSCs preferentially accumulate within lung tissues after systemic administration into accounts, the tumor-tropic MSCs/NPs system is feasible and promising for targeted RT treatment of NSCLC.

Keywords: MSC-mediated delivery; nano-radiosensitizers; non-small cell lung cancer; radiotherapy; targeting.