Safe and Effective Delivery of Antitumor Drug Using Mesenchymal Stem Cells Impregnated with Submicron Carriers

Alexander S. Timin, Oleksii O. Peltek, Mikhail V. Zyuzin, Albert R. Muslimov, Timofey E. Karpov, Olga S. Epifanovskaya, Alena I. Shakirova, Mikhail V. Zhukov, Yana V. Tarakanchikova, Kirill V. Lepik, Vladislav S. Sergeev, Gleb B. Sukhorukov, Boris V. Afanasyev

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)13091-13104
Number of pages14
JournalACS Applied Materials and Interfaces
Volume11
Issue number14
DOIs
Publication statusPublished - 10 Apr 2019

Keywords

  • human mesenchymal stem cells
  • malignant tumor
  • silica capsules
  • spontaneous and directed migration
  • tumor spheroid
  • tumor therapy
  • vincristine

ASJC Scopus subject areas

  • Materials Science(all)

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  • Cite this

    Timin, A. S., Peltek, O. O., Zyuzin, M. V., Muslimov, A. R., Karpov, T. E., Epifanovskaya, O. S., Shakirova, A. I., Zhukov, M. V., Tarakanchikova, Y. V., Lepik, K. V., Sergeev, V. S., Sukhorukov, G. B., & Afanasyev, B. V. (2019). Safe and Effective Delivery of Antitumor Drug Using Mesenchymal Stem Cells Impregnated with Submicron Carriers. ACS Applied Materials and Interfaces, 11(14), 13091-13104. https://doi.org/10.1021/acsami.8b22685