Cryo-Trojan Mesenchymal Stem Cells as Non-Living Tumor-Homing Supercarriers for Enhanced Drug Delivery and Immune Activation in Prostate Cancer

Materials Today Bio, Journal Year: 2025, Volume and Issue: 32, P. 101650 - 101650

Published: March 12, 2025

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. 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 chemokine receptors (CXCR4/CCR2) targeting eliminating proliferative risks. Comprehensive evaluations included loading/release kinetics, in vitro suppression, immunogenic cell death (ICD) induction, vivo efficacy/safety prostate models. CT-MTX demonstrated superior loading (116.38 μg/106 cells) pH-sensitive release (74.10 % at pH 5.5), outperforming exosomes, liposomes, living MSCs stability tumor-specific delivery. Compared to liposomes (low targeting) nanomaterials (biocompatibility concerns), leveraged MSC-derived tropism without tumorigenic In vitro, inhibited proliferation (84.83 MTX uptake), migration (4.42 residual migration), induced apoptosis (43.23 late apoptosis). Mechanistically, triggered ICD via PAMPs release, activating CD8+ T suppressing immunosuppressive Treg. vivo, selectively accumulated tumors, reducing growth 87.88 extending survival (93.30 vs. 66.70 controls) negligible toxicity. Proteomics revealed enriched immune pathways like NK cytotoxicity, validating its dual role direct killing activation. represents novel, non-proliferative platform combines the capacity enhanced safety controlled inducing ICDs other immunologically "cold" tumors improve infiltration.

Language: Английский

Benign non-immune cells in tumor microenvironment

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 3, 2025

The tumor microenvironment (TME) is a highly complex and continuous evolving ecosystem, consisting of diverse array cellular non-cellular components. Among these, benign non-immune cells, including cancer-associated fibroblasts (CAFs), adipocytes, endothelial cells (ECs), pericytes (PCs), Schwann (SCs) others, are crucial factors for development. Benign within the TME interact with both immune cells. These interactions contribute to progression through direct contact indirect communication. Numerous studies have highlighted role that exert on potential tumor-promoting mechanisms via multiple signaling pathways factors. However, these may play different roles across cancer types. Therefore, it important understand based heterogeneity. A deep understanding allows us develop novel therapies by targeting In this review, we will introduce several types according heterogeneity their in TME.

Language: Английский