Mesenchymal stem cell-mediated theranostic delivery system

Abstract

Nanotechnology offers the means to improve current cancer detection and therapy as well as might lead to permanent elimination of cancer while reducing damage to healthy tissues. However, one of the main hurdles nanoparticles (NPs) must overcome is their low accumulation in tumors. Mesenchymal stem cells (MSCs) have inherent tumor-tropic properties and thus could be used as anti-cancer “Trojan horses” delivering theranostic NPs directly into tumor. Previously we have shown that photoluminescent semiconductor NPs called quantum dots (QDs) do not affect the properties of MSCs and, most importantly, QD-loaded MSCs migrate specifically toward cancer cells both in vitro and in vivo while avoiding healthy tissues. To test the therapeutic potential of this delivery system, we have constructed a complex composed of QDs and a second-generation photosensitizer (PS) chlorin e6 (Ce6). Such complex combines both cancer diagnostic and therapeutic properties. QD-Ce6 complexes generate reactive oxygen species (ROS) without direct excitation of PS – upon both linear and non-linear excitation, enabling excitation in tissue transparency window, QDs serve as donors and transfer energy to Ce6 via Förster resonance energy transfer (FRET). In this study the spectral properties, size, and zeta potential of QD-Ce6 complex were measured. The stability of the complex in cell culture media and the impact of serum proteins were evaluated. Finally, MSC and cancer cell response to QD-Ce6 complex were determined.