Journal
MOLECULES
Volume 27, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/molecules27082419
Keywords
mesenchymal stem cells; hyaluronic acid; poly (lactide-co-glycolide); orthotopic glioma; tumor penetration
Funding
- National Natural Science Foundation of China [81402872]
- Public Welfare Technology Research Project of Zhejiang [LGF21H300001]
- Hangzhou Science and Technology Foundation of China [20191203B48]
- second round of the excellent innovation team of Hangzhou Municipal University
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By utilizing the tumor-targeting property of MSCs, a drug delivery system was developed to improve drug transfer in tumor cells and achieve deep tumor penetration, leading to better therapeutic outcomes.
Tumor penetration and the accumulation of nanomedicines are crucial challenges in solid tumor therapy. By taking advantage of the MSC tumor-tropic property, we developed a mesenchymal stem cell (MSC)-based drug delivery system in which paclitaxel (PTX)-encapsulating hyaluronic acid-poly (D,L-lactide-co-glycolide) polymeric micelles (PTX/HA-PLGA micelles) were loaded for glioma therapy. The results indicated that CD44 overexpressed on the surface of both MSCs and tumor cells not only improved PTX/HA-PLGA micelle loading in MSCs, but also promoted the drug transfer between MSCs and adjacent cancer cells. It was hypothesized that CD44-mediated transcytosis played a crucial role and allowed deep glioma penetration depending on sequential intra-intercellular delivery via endocytosis-exocytosis. MSC-micelles were able to infiltrate from normal brain parenchyma towards contralateral tumors and led to the eradication of glioma. The survival of orthotopic glioma-bearing rats was significantly extended. In conclusion, the MSC-based delivery of HA-PLGA micelles is a potential strategy for tumor-targeting drug delivery.
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