Recent advances in nanomedicine have facilitated the development of potent nanomaterials with intrinsic enzyme-like activities (nanozymes) for cancer therapy. However, it remains a great challenge to fabricate smart nanozymes that precisely perform enzymatic activity in tumor microenvironment without inducing off-target toxicity to surrounding normal tissues. Herein, we report on designed fabrication of biodegradation-medicated enzymatic activity-tunable molybdenum oxide nanourchins (MoO3–x NUs), which selectively perform therapeutic activity in tumor microenvironment via cascade catalytic reactions, while keeping normal tissues unharmed due to their responsive biodegradation in physiological environment. Specifically, the MoO3–x NUs first induce catalase (CAT)-like reactivity to decompose hydrogen peroxide (H2O2) in tumor microenvironment, producing a considerable amount of O2 for subsequent oxidase (OXD)-like reactivity of MoO3–x NUs; a substantial cytotoxic superoxide radical (·O2 –) is thus generated for tumor cell apoptosis. Interestingly, once exposed to neutral blood or normal tissues, MoO3–x NUs rapidly lose the enzymatic activity via pH-responsive biodegradation and are excreted in urine, thus ultimately ensuring safety. The current study demonstrates a proof of concept of biodegradation-medicated in vivo catalytic activity-tunable nanozymes for tumor-specific cascade catalytic therapy with minimal off-target toxicity.

Fatty acid amide hydrolase (FAAH) overexpression induces several disorder symptoms in nerve systems, and therefore long-term tracing of FAAH activity in vivo is of high importance but remains challenging. Current bioluminescence (BL) methods are limited in detecting FAAH activity within 5 h. Herein, by rational design of a latent BL probe (d-Cys-Lys-CBT)2 (1), we developed a "smart" method of intracellular reduction-controlled self-assembly and FAAH-directed disassembly of its cyclic d-luciferin-based nanoparticles (i.e., 1-NPs) for persistent BL imaging of FAAH activity in vitro, in cells, and in vivo. Using aminoluciferin methyl amide (AMA), Lys-amino-d-luciferin (Lys-Luc), and amino-d-luciferin (NH2-Luc) as control BL probes, we validated that the persistent BL of 1 from luciferase-expressing cells or tumors was controlled by the activity of intracellular FAAH. With the property of long-term tracing of FAAH activity in vivo of 1, we envision that our BL precursor 1 could probably be applied for in vivo screening of FAAH inhibitors and the diagnosis of their related diseases (or disorders) in the future.

His current research interests include Environmental Impact Assessment, Toxicity, Waste Management, and Electrochemical applications. He has worked in various government-funded and consulting projects at NTU. He is trained in Life Cycle Assessment tools such as GaBi and SimaPro, Nanotools such as AFM, Ellipsometry, ATR-FTIR and QCMD, USEtox® 2.0-Characterization fact. Liya Ge obtained her B.Eng. in chemical engineering from Zhejiang University, China in 1999. From 1999-2002, she worked as an Engineer in State Oceanic Administration, China. She subsequently completed her PhD study in analytical chemistry from Nanyang Technological University (NTU), Singapore in 2005. Since then, Dr. Ge has been working as a researcher and later a senior researcher in NTU. Her current research interests cover analytical chemistry including the development of sensors, biosensors and micro total analysis systems for rapid on-site detection and point-of-care diagnosis. Xiaoxu Fu is currently a PhD student at the School of Civil and Environmental Engineering at Nanyang Technological University (NTU), Singapore. He got his master degree in the same school in NTU and his bachelor degree in Shanghai Jiao Tong university in China. His scienfic research and interest is focused on conducting polymers and their application on biomedical, analytical and environmental applications. Grzegorz Lisak obtained his M.Sc. (Chem. Eng.) in physical chemistry in 2007 from Poznań University of Technology, Poland. He obtained his D.Sc. (Tech.

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