An
important area in modern malignant tumor therapy is the optimization
of 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 focuses 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 the antitumor
drug doxorubicin) into nano- and microcarriers with their further
association into therapeutically relevant cells that possess the ability
to migrate to sites of tumor. Here, we fundamentally examine the effect
of drug carrier size on the behavior of human mesenchymal stem cells
(hMSCs), including 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 three-dimensional spheroid model in collagen
gel. Compared to free VCR, the developed hMSC-based drug delivery
platform showed enhanced antitumor activity regarding those tumors
that express CXCL12 (stromal cell-derived factor-1 (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.