Mesenchymal stem cells as delivery vehicles of photosensitizer functionalized nanoparticles: cell therapy meets nanotechnology

Abstract

Regardless the progress made, cancer therapies are not effective enough yet. Nanotechnology has emerged as one of the most promising solutions to permanent elimination of cancer. Because of the exceptional physicochemical properties and large surface area, which enables conjugation of various molecules, nanoparticles (NPs) quickly gained much attention in oncology. However, NPs themselves lack specificity to tumors. Due to their inherent tissue regeneration function, mesenchymal stem cells (MSCs) are naturally attracted to inflammations and wounds, as well as tumors, and thus could be used in cell-mediated transportation of NPs. Previously we have proven that photoluminescent NPs called quantum dots (QDs) do not affect the properties of MSCs1 and that MSCs are able to specifically migrate toward tumor cells both in vitro and in vivo while avoiding healthy tissues2. In this study, we have constructed a complex composed of QDs and a second-generation photosensitizer (PS) chlorin e6 (Ce6) to obtain multifunctional NPs, combining both cancer diagnostic and therapeutic properties. Such complex allows us to induce generation of reactive oxygen species (ROS) without direct excitation of PS as excited QDs transfer energy to Ce6 via Förster resonance energy transfer (FRET)3. 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 tested.