Stem cell-based delivery of theranostic nanoparticles to cancer cells

Abstract

Advances in nanotechnologies have provided the promising potential of cancer elimination. Owing to nanosize, nanomaterials gain exceptional physicochemical properties such as magnetic properties or bright luminescence, while large surface area enables conjugation of various diagnostic and therapeutic molecules. Such multifunctional nanoparticles gain increasing attention in oncology. However, nanoparticles themselves usually lack specificity to tumors. Therefore, cellular Trojan horses were proposed. Mesenchymal stem cells (MSCs) possess selfrenewal and immunomodulatory properties and participate in wound healing, bone regeneration, angiogenesis, and homeostasis. Due to these characteristics, MSCs hold great promise in the treatment of wounds, degenerative diseases, and other pathologies. Moreover, MSCs have a tendency to migrate selectively toward tumor cells and thus could be used as nanoparticle delivery vehicles. We were the first ones to investigate skin-derived MSCs in such theranostic delivery system. First, we tested tumor-tropic properties of quantum dot (QD)-loaded MSCs in both in vitro and in vivo, and proven MSC cancer-specific migration efficacy. To test the therapeutic potential, we have constructed a complex composed of QDs and a second-generation photosensitizer (PS) chlorin e6 (Ce6) to obtain m ultifunctional nanoparticles. QD-Ce6 complexes generate reactive oxygen species (ROS) without direct excitation of PS upon both linear and non-linear twophoton excitation, thus enabling excitation in optical tissue transparency window. 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.