Journal Article Epublish 1 citation
PubMed: 40151804 DOI: 10.1016/j.mtbio.2025.101650
Cryo-trojan mesenchymal stem cells as non-living tumor-homing supercarriers for enhanced drug delivery and immune activation in prostate cancer.
Mater Today Bio 32:101650
Authors: Chengran Wang, Xinao Rong, Fuqiang Zhang, Xupeng Mu, Jinlan Jiang
Affiliations
- Department of Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, China.
Abstract
Background
Prostate cancer remains a leading cause of cancer-related mortality, with conventional therapies limited by systemic toxicity and poor tumor targeting. Developing innovative drug delivery systems that enhance therapeutic specificity while minimizing off-target effects is critical.
Materials and methods
We engineered cryo-trojan human umbilical cord mesenchymal stem cells (CT-MSCs) as non-living, tumor-homing carriers for mitoxantrone (MTX), termed CT-MTX. Cryo-treatment preserved structural integrity and chemokine receptors (CXCR4/CCR2) for tumor targeting while eliminating proliferative risks. Comprehensive evaluations included drug loading/release kinetics, tumor suppression, immunogenic cell death (ICD) induction, and in vivo efficacy/safety in prostate cancer models.
Results
CT-MTX demonstrated superior drug loading (116.38 μg/10 cells) and pH-sensitive release (74.10 % at pH 5.5), outperforming exosomes, liposomes, and living MSCs in stability and tumor-specific drug delivery. Compared to liposomes (low targeting) and nanomaterials (biocompatibility concerns), CT-MTX leveraged MSC-derived tropism without tumorigenic risks. In vitro, CT-MTX inhibited tumor proliferation (84.83 % MTX uptake), migration (4.42 % residual migration), and induced apoptosis (43.23 % late apoptosis). Mechanistically, CT-MTX triggered ICD via PAMPs release, activating CD8 T cells and suppressing immunosuppressive Treg. In vivo, CT-MTX selectively accumulated in tumors, reducing growth by 87.88 % and extending survival (93.30 % vs. 66.70 % in controls) with negligible systemic toxicity. Proteomics revealed enriched immune pathways like NK cell cytotoxicity, validating its dual role in direct tumor killing and immune activation.
Conclusion
CT-MTX represents a novel, non-proliferative drug delivery platform that combines the tumor-homing capacity of MSCs with enhanced safety and controlled release, inducing ICDs for prostate cancer and other immunologically "cold" tumors to improve immune infiltration.
MeSH
Cells, Safety, Microscopy, Electron, Scanning Transmission, Pharmaceutical Preparations, Liposomes, Neoplasms, Prostate, Stem Cells, Mesenchymal Stem Cells, Prostatic Neoplasms, Therapeutics, Apoptosis