期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 59, 期 49, 页码 22054-22062出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202001469
关键词
cancer therapy; hypoxia prodrugs; lactate oxidase; mesoporous silica nanoparticles; tumor microenvironment
资金
- Australian Research Council
- Queensland node of the Australian National Fabrication Facility
- Australian Microscopy and Microanalysis Research Facility at the Centre for Microscopy and Microanalysis
- University of Queensland
- Science and Technology Commission of Shanghai Municipality, China [19JC1412100]
The direct depletion of lactate accumulated in the tumor microenvironment holds promise for cancer therapy but remains challenging. Herein, we report a one-pot synthesis of openwork@ dendritic mesoporous silica nanoparticles (ODMSNs) to address this problem. ODMSNs self-assembled through a time-resolved lamellar growth mechanism feature an openworked core and a dendritic shell, both constructed by silica nanosheets of approximate to 3 nm. With a large pore size, high surface area and pore volume, ODMSNs exhibited a high loading capacity (>0.7 g g(-1)) of lactate oxidase (LOX) and enabled intratumoral lactate depletion by >99.9 %, leading to anti-angiogenesis, down-regulation of vascular endothelial growth factor, and increased tumor hypoxia. The latter event facilitates the activation of a co-delivered prodrug for enhancing anti-tumor and anti-metastasis efficacy. This study provides an innovative nano-delivery system and demonstrates the first example of direct lactate-depletion-enabled chemotherapy.
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