Gold nanoparticles (AuNPs) with simultaneous plasmonic and biocatalytic properties provide a promising approach to developing versatile bioassays. However, the combination of AuNPs' intrinsic enzyme-mimicking properties with their surface-enhanced Raman scattering (SERS) activities has yet to be explored. Here we designed a peroxidase-mimicking nanozyme by in situ growing AuNPs into a highly porous and thermally stable metal-organic framework called MIL-101. The obtained AuNPs@MIL-101 nanozymes acted as peroxidase mimics to oxidize Raman-inactive reporter leucomalachite green into the active malachite green (MG) with hydrogen peroxide and simultaneously as the SERS substrates to enhance the Raman signals of the as-produced MG. We then assembled glucose oxidase (GOx) and lactate oxidase (LOx) onto AuNPs@MIL-101 to form AuNPs@MIL-101@GOx and AuNPs@MIL-101@LOx integrative nanozymes for in vitro detection of glucose and lactate via SERS. Moreover, the integrative nanozymes were further explored for monitoring the change of glucose and lactate in living brains, which are associated with ischemic stroke. The integrative nanozymes were then used to evaluate the therapeutic efficacy of potential drugs (such as astaxanthin for alleviating cerebral ischemic injuries) in living rats. They were also employed to determine glucose and lactate metabolism in tumors. This study not only demonstrated the great promise of combining AuNPs' multiple functionalities for versatile bioassays but also provided an interesting approach to designing nanozymes for biomedical and catalytic applications.

Nanozymes, the nanostructures with enzymatic activities, have attracted considerable attention because, in comparison with natural enzymes, they offer the possibility of lowered cost, improved stability, and excellent recyclability. However, the specificity and catalytic activity of current nanozymes are still far lower than that of their natural counterparts, which in turn has limited their use such as in bioanalysis. To address these challenges, herein we report the design and development of integrated nanozymes (INAzymes) by simultaneously embedding two cascade catalysts (i.e., a molecular catalyst hemin and a natural enzyme glucose oxidase, GOx) inside zeolitic imidazolate framework (ZIF-8) nanostructures. Such integrated design endowed the INAzymes with major advantage in improved catalytic efficiency as the first enzymatic reaction occurred in close (nanoscale) proximity to the second enzyme, so products of the first reaction can be used immediately as substrates for the second reaction, thus overcoming the problems of diffusion-limited kinetics and product instability. The considerable high catalytic activity and stability enabled the INAzymes to efficiently draw a colorimetric detection of glucose with good sensitivity and selectivity. When facilitated with in vivo microdialysis, the INAzyme was successfully used for facile colorimetric visualization of cerebral glucose in the brain of living rats. Moreover, when further combined with microfluidic technology, an integrative INAzyme-based online in vivo analytical platform was constructed. The promising application of the platform was successfully illustrated by continuously monitoring the dynamic changes of striatum glucose in living rats' brain following ischemia/reperfusion. This study developed a useful approach to not only functional nanomaterial design but also advanced platforms developments for diverse targets monitoring.

The design of a delivery system was reported based on stimuli-responsive poly(N-isopropylacrylamide) (PNIPA) inside a mesostructured cellular foam (MCF) via atom transfer radical polymerization (ATRP), and the control of drug release in response to the environmental temperature was investigated. The successful synthesis of PNIPA inside the MCF was confirmed by Fourier transform infrared (FT-IR), transmission electron microscopy (TEM) and nitrogen adsorption/desorption measurements. Control of drug release through the porous network was performed by measuring the uptake and release of ibuprofen (IBU). The delivery system of MCF-PNIPA demonstrated a high IBU storage capacity of 58 wt% (IBU/silica), which is much higher than that reported for functional SBA-15 (37 wt%). The multilayer polymers inside the pores of the MCF were considered to form an internal cavity for drug molecules in addition to responding to changes in external temperature.

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Although ultrasmall metal nanoparticles (NPs) have been used as radiosensitizers to enhance the local damage to tumor tissues while reducing injury to the surrounding organs, their rapid clearance from the circulatory system and the presence of hypoxia within the tumor continue to hamper their further application in radiotherapy (RT). In this study, we report a size tunable nanocluster bomb with a initial size of approximately 33 nm featuring a long half-life during blood circulation and destructed to release small hypoxia microenvironment-targeting NPs (∼5 nm) to achieve deep tumor penetration. Hypoxic profiles of solid tumors were precisely imaged using NP-enhanced computed tomography (CT) with higher spatial resolution. Once irradiated with a 1064 nm laser, CT-guided, local photothermal ablation of the tumor and production of radical species could be achieved simultaneously. The induced radical species alleviated the hypoxia-induced resistance and sensitized the tumor to the killing efficacy of radiation in Akt-mTOR pathway-dependent manner. The therapeutic outcome was assessed in animal models of orthotopical breast cancer and pancreatic cancer, supporting the feasibility of our combinational treatment in hypoxic tumor management.