Perpustakaan Digital ITB

An important area in modern malignant tumor therapy is theoptimization of antitumor drugs pharmacokinetics. The use of someantitumor drugs is limited in clinical practice due to their high toxicity.Therefore, the strategy for optimizing the drug pharmacokinetics focuses onthe generation of high local concentrations of these drugs in the tumor areawith minimal systemic and tissue-specific toxicity. This can be achieved byencapsulation of highly toxic antitumor drug (vincristine (VCR) that is 20?50 times more toxic than widely used the antitumor drug doxorubicin) intonano- and microcarriers with their further association into therapeuticallyrelevant cells that possess the ability to migrate to sites of tumor. Here, wefundamentally examine the effect of drug carrier size on the behavior ofhuman mesenchymal stem cells (hMSCs), including internalizationefficiency, cytotoxicity, cell movement, to optimize the conditions for thedevelopment of carrier-hMSCs drug delivery platform. Using the malignant tumors derived from patients, we evaluated thecapability of hMSCs associated with VCR-loaded carriers to target tumors using a three-dimensional spheroid model in collagengel. Compared to free VCR, the developed hMSC-based drug delivery platform showed enhanced antitumor activity regardingthose tumors that express CXCL12 (stromal cell-derived factor-1 (SDF-1)) gene, inducing directed migration of hMSCs viaCXCL12 (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 andlow systematic toxicity, revealing novel strategies for chemotherapy in the future.