Safe and effective delivery of antitumor drug using mesenchymal stem cells impregnated with submicron carriers.

An important area in modern malignant tumor therapy is the optimization of the antitumor drugs pharmacokinetics. The use of some antitumor drugs is limited in clinical practice due to their high toxicity. Therefore, the strategy for optimizing the drug pharmacokinetics is focusing on the generation of high local concentrations of these drugs in the tumor area with minimal systemic and tissue-specific toxicity. This can be achieved by encapsulation of highly toxic antitumor drug (vincristine/VCR that is 20-50 times more toxic than widely used in antitumor therapy doxorubicin) into nano- and microcarriers with their further association into therapeutically relevant cells that possess ability to migrate to sites of tumor. Here we fundamentally examine the effect of drug carrier size on behavior of human mesenchymal stem cells (hMSCs), incl. internalization efficiency, cytotoxicity, cell movement, to optimize the conditions for the development of carrier-hMSCs drug delivery platform. Using the malignant tumors derived from patients, we evaluated the capability of hMSCs associated with VCR loaded carriers to target tumors using a 3D spheroid model in collagen gel. Compared to free VCR, developed hMSCs-based drug delivery platform showed enhanced antitumor activity regarding to those tumors that express CXCL12 (SDF-1) gene, inducing directed migration of hMSCs via CXCL12 (SDF-1)/CXCR4 pathway. These results show that the combination of encapsulated antitumor drugs and hMSCs, which possess the properties of active migration into tumors, is therapeutically beneficial and demonstrated high efficiency and low systematic toxicity, revealing novel strategies for chemotherapy in the future.