Mesenchymal Stem Cells Membrane Biomimetic Nanoplatform for Glioblastoma-Targeted Combinatorial Chemotherapy

Glioblastoma, the most aggressive form of brain tumor, continues to present significant therapeutic challenges, including the limited delivery of drugs posed by the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB), severe systemic toxicity associated with conventional chemotherapy, and the complexity arising from tumor heterogeneity.

To overcome these challenges, this study developed a novel biomimetic drug delivery system. Specifically, we prepared poly(lactic-co-glycolic acid) (PLGA) nanoparticles co-loaded with the chemotherapeutic agent doxorubicin (DOX) and the natural polyphenol curcumin (CUR), and subsequently functionalized them with the membrane of human umbilical cord mesenchymal stem cells (hUC-MSCs), which possess inherent tumor-homing capability.

In vitro studies demonstrated that the hUC-MSCs membrane coating significantly enhanced targeted recognition and cellular uptake by glioblastoma cells, and the biomimetic nanoplatform exhibited superior synergistic cytotoxicity and induced greater cellular apoptosis compared to free drug combinations and uncoated nanoparticles. Antitumor mechanism analysis indicated that biomimetic nanoplatform inhibited glioblastoma migration, invasion, and angiogenesis. In vivo anti-tumor efficacy studies showed that the biomimetic nanoparticles effectively suppressed the growth of tumor. Notably, CUR contributed to the system by amplifying the anticancer activity of DOX and alleviating its associated toxicity.

This work demonstrates that hUC-MSC membrane-camouflaged PLGA nanoparticles enable successful co-delivery of DOX and CUR, offering a promising strategy to address the critical barriers of delivery and toxicity in GBM chemotherapy, supported by their excellent in vitro targeting, in vivo anti-tumor efficacy, and reduced toxicity profile.