Hitchhiking nanoparticles: prospects of stem cell use in cancer theranostics

Abstract

Nanoparticles have long been considered for various biomedical and therapeutic applications, for example, as drug carriers or medical imaging contrast agents. Semiconductor quantum dots (QDs) have unique size-dependent optical properties and are used in biological and medical research, including photodynamic therapy (PDT). For instance, QDs could serve as Förster resonance energy transfer (FRET) donors to photosensitizers (PS) which can easily intercalate within the coating of QDs and foster favorable conditions for effective FRET to occur. Such QD-PS complexes circumvent the disadvantages of classical PS and thus could increase the overall PDT efficacy. Our research revealed that the nature of nanoparticle amphiphilic coating greatly influences QD-PS complex formation, as well as accumulation in cancer cells and PDT efficiency [1]. QD-PS complexes could potentially be used in an indirect mediation of PDT and cancer eradication, although selective accumulation of nanoparticles in cancerous tissue remains one of the unresolved issues of cancer research. Multiple strategies increasing the accumulation of theranostic nanoparticles in tumor were proposed – passive accumulation due to enhanced permeability and retention (EPR) effect, functionalization with targeting moieties, or cell-based delivery. Mesenchymal stem cell (MSC) innate tumor tropism allows them to be used as “Trojan horses” delivering theranostic NPs selectively to tumor. Tumor tropic characteristics of MSCs were proven in both in vitro and in vivo experiments. To test the therapeutic potential of stem cell-based system, multifunctional complex composed of QDs and a second-generation photosensitizer chlorin e6 (Ce6) was proposed. Physicochemical properties, stability of the complex in cell culture media and the impact of serum proteins were evaluated. QD-Ce6 complex and blue light showed up to 100% therapeutic effect on MSCs and cancer cells. Following successful in vitro experiments, pilot in vivo experiment using theranostic complex-loaded MSCs was performed on tumor bearing mice and their survival after PDT treatment was tracked – MSC-mediated delivery of QD-Ce6 complex and PDT reduced tumor growth and prolonged the survival of mice.