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Openwork@Dendritic Mesoporous Silica Nanoparticles for Lactate Depletion and Tumor Microenvironment Regulation
Author(s) -
Tang Jie,
Meka Anand Kumar,
Theivendran Shevanuja,
Wang Yue,
Yang Yannan,
Song Hao,
Fu Jianye,
Ban Wenhuang,
Gu Zhengying,
Lei Chang,
Li Shumin,
Yu Chengzhong
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202001469
Subject(s) - tumor microenvironment , mesoporous silica , chemistry , tumor hypoxia , angiogenesis , prodrug , nanoparticle , biophysics , nanotechnology , mesoporous material , cancer research , materials science , biochemistry , catalysis , tumor cells , biology , medicine , radiation therapy
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 ≈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.