@article{Zhao2025, 
author = {Hanqin Zhao and Yuxi Gao and Sheng Ma and Xinghui Si and Jiaxuan Li and Yibo Qi and Zichao Huang and Yu Zhang and Tianmeng Sun and Lingyu Li and Wantong Song and Xuesi Chen},
title = {Hyaluronidase nanogel-armed CAR-T cell for synergistically reducing tumor extracellular matrix and improving efficacy against solid tumors},
year = {2025},
journal = {Nano Research},
volume = {18},
number = {5},
pages = {94907359},
keywords = {immunotherapy, CAR-T cell therapy, nanogels, metabolic oligosaccharide labelling},
url = {https://www.sciopen.com/article/10.26599/NR.2025.94907359},
doi = {10.26599/NR.2025.94907359},
abstract = {The application of chimeric antigen receptor T (CAR-T) cell therapy against solid tumors is often hindered by the dense and rigid tumor extracellular matrix (ECM). While combining CAR-T with hyaluronidase (HAase) to reduce ECM is apparent, the efficacy is limited because of low accumulation and penetration efficiency of HAase inside the tumor tissue. Herein, we report a stimuli-responsive HAase-loaded nanogels (H-NGs) which are conjugated on the surface of CAR-T cells for synergistically improving HAase accumulation, ECM degradation and CAR-T cell efficacy. The conjugation of H-NGs on the T cell surface was achieved through metabolic oligosaccharide engineering (MOE) in a semi-quantitatively controlled manner. Intravenous injection of H-NGs armed CAR-T cells resulted in more ECM degradation than co-injection of CAR-T cells and free H-NGs, leading to an 83.2% tumor inhibition rate and relieving tumor suppressive microenvironment in the Raji solid tumor model. Proteomic analysis of the harvested tumor tissues indicated that the combining of H-NGs and CAR-T cell collaboratively reduces cell adhesion and enhanced leukocyte transendothelial migration. Overall, this work simultaneously boosts the efficacy of hyaluronidase and CAR-T cells in combating solid tumor, which has broad application potential in cancer combination therapy.}
}