| Abstract [eng] |
The lack of early cancer diagnosis and poor selectivity of chemotherapeutic drugs are among the main challenges of oncology. Photosensitizer and nanoparticle complexes can become a theranostic platform for solving current cancer diagnosis and treatment problems by combining diagNOSTIC and THERApeutic properties. However, nanoparticles and their complexes do not provide sufficient specificity for tumors, thus mesenchymal stem cells (MSCs) with innate oncotropism can be used to transport theranostic nanoparticles. The aim of this work is to investigate the ability of skin MSCs to selectively transport theranostic nanoparticles to tumors, ensuring therapeutic effects and diagnostic potential. The theranostic nanocomplex is composed of photoluminescent nanoparticles quantum dots (QDs) and photosensitizer chlorin e6 (Ce6). In this dissertation, passive delivery of nanoparticles to tumors was found to be non-specific and inefficient, thus justifying the need to use MSCs. It was also assessed that the most suitable for complex formation with Ce6 are amphiphilic polymer coated and carboxyl functionalized QDs. Our research has shown that such a complex effectively generates singlet oxygen when excited by a specific 470 nm wavelength light, but we demonstrated for the first time that serum proteins quickly destabilize the complex and significantly reduce its efficiency. In in vitro studies, we have shown that nanoparticles are biocompatible and accumulate in the MSCs in endocytic vesicles, where the QD-Ce6 complex is protected from the negative effects of serum proteins and remains stable. In vitro and in vivo studies have proven that MSCs are able to transport theranostic nanoparticles selectively to cancer cells, to label tumors with visible photoluminescence, and cause cancer cell death during two-step irradiation procedure. The combined therapy of MSCs, QD-Ce6 complex, and non-toxic light significantly increases survival, reduces tumor growth, metastatic potential and overall cancer progression. Our results confirm that MSCs with QD-Ce6 complex can be applied in cancer theranostics. |
