Adv Mater. 2022 Jan;34(4):e2106010. doi: 10.1002/adma.202106010.

Tumor-Microenvironment-Activated Reactive Oxygen Species Amplifier for Enzymatic Cascade Cancer Starvation/Chemodynamic /Immunotherapy.

Man Wang, Mengyu Chang, Chunxia Li, Qing Chen, Zhiyao Hou, Bengang Xing, Jun Lin

1 Institute of Molecular Sciences and Engineering, Institute of Frontier and Interdisciplinary Science, Shandong University, Qingdao, 266237, P. R. China.

2 State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.

3 Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Xinzao Town, Panyu District, Guangzhou, Guangdong, 511436, P. R. China.

4 School of Physical & Mathematical Sciences, Nanyang Technological University, Singapore, 639798, Singapore.

At present, some progress has been made in the field of cancer theranostics based on nanocatalysts (NCs), but achieving precise theranostics in response to the specific tumor microenvironment (TME) remains a major challenge. Herein, a TME-responsive upconversion nanoparticles (UCNPs)-based smart UCNPs@Cu-Cys-GOx (UCCG) nanosystem is engineered, which combines natural enzymes and nanozymes so as to amplify reactive oxygen species (ROS) generation in situ for cancer starvation/chemodynamic/immunotherapy. One of the biggest merits of this material is that it can be preserved inert (off) in normal tissues, and only in the TME can it be specifically activated (on) through a series of enzymatic cascades to boost ROS production via a strategy of open source (H2 O2 self-supplying ability) and reduce expenditure (glutathione (GSH) consuming ability). More importantly, the enhanced oxidative stress by UCCG NCs reverses the immunosuppressive TME, and facilitates antitumor immune responses. Meanwhile, the starvation/chemodynamic synergistic therapy triggered by UCCG combined with PD-L1 antibody effectively inhibits the growth of primary tumors and cancer metastasis. In addition, the UCNPs in UCCG present upconversion luminescence enhancement, which can be exploited to visualize the reinforced ROS generation in real time. Collectively, this work provides an original method for the devising and exploitation of UCNPs-based catalytic immunotherapy.

文章链接https://onlinelibrary.wiley.com/doi/10.1002/adma.202106010