The homeostasis of ascorbic acid (AA) plays vital roles in the brain, which relies on in vivo real-time concentration monitoring to uncover its correlation to neurological functions and diseases. Electrochemical sensing with carbon fiber electrodes (CFEs) offers high spatiotemporal resolution and sensitivity for in vivo sensing of AA but faces challenges such as electrode fouling by oxidation byproducts and interference from coexisting neurochemicals. Here, we report the design of metalloporphyrin-based olefin-conjugated covalent organic frameworks (COFs) that synergize atomically dispersed M-N₄ catalytic sites, hierarchical porosity, and π-conjugated conductivity to enhance AA oxidation kinetics while eliminating interference. We show that nickel porphyrin COFs-modified CFE gains exceptional sensitivity (4.44×10⁻³ μA·μM⁻¹), stability (negligible signal decay over 4000 s), and selectivity in rat brain, enabling real-time tracking of stimulus-evoked AA release during spreading depolarization. This study demonstrates the potential of COFs as a reliable platform for implementing implantable sensing technologies for accurate neurochemical profiling in complex networks.

The safety of nanoparticle-based drug delivery systems (DDSs) for cancer treatment is still a challenge, restricted by the intrinsic cytotoxicity of drug carriers and leakage of loaded drug. Here, we propose a novel nanocarrier’s cytotoxicity avoidance strategy by synthesizing an encapsulation core–shell structure of zeolitic imidazolate framework-8 (ZIF-8)-based colloid particles (CPs) with an amorphous ZIF-8 skin. This encapsulation structure achieves an ultra-high loading rate (LR) of 90% (i.e., 9 mg doxorubicin (DOX) per 1 mg ZIF-8) for DOX and the protection of DOX from leaking. Notably, to deliver unit-dose drug, this ultra-high LR of 90% significantly reduces the usage of ZIF-8 to 1.2% (2 orders of magnitude) compared to that of DOX@ZIF-8 with a 10% LR, in which cytotoxicity of ZIF-8 could well below the safety limit and then be relatively ignored. Safety, drug delivery efficacy, scale-up ability, and universality of this encapsulation structure have been further verified. Our findings suggest the great potential of this ZIF-8-based encapsulation core–shell structure in the field of drug delivery.

Modulating electronic structure of metal nanoparticles via metal–support interaction has attracted intense interest in the field of catalytic science. However, the roles of supporting substrates in regulating catalytic properties of nanozymes remain elusive. In this study, we find that the use of graphdiyne oxide (GDYO) as the substrate for self-terminating growth of Ru nanoparticles (Ru@GDYO) endows the peroxidase-like activity of Ru nanoparticles with intrinsic physiological pH preference and natural horseradish peroxidase (HRP) comparable performance. Ru nanoparticles electrolessly deposited onto GDYO possess a partially oxidized electronic structure owing to limited charge transfer between Ru and GDYO, contributing to the intrinsic physiological pH preference of the peroxidase-mimicking nanozyme. More importantly, the substrate GDYO plays an influential factor in enhancing catalytic activity, that is, the activity of Ru@GDYO is much higher than that of Ru nanoparticles deposited on other carbon substrates including graphene oxides and graphdiyne. To demonstrate the application of Ru@GDYO nanozyme in neutral solutions, we employ Ru@GDYO with nicotinamide adenine dinucleotide (NAD⁺)-dependent dehydrogenases in physiological conditions to realize a sustainable cascade reaction by means of forming continuous NAD⁺/dihydronicotiamide adenine dinucleotide (NADH) recycling. Our finding represents a promising perspective on designing high-performance peroxidase-mimicking nanozymes with broader applicability, raising fundamental understanding of structure–activity relationship, and investigating new applications of nanozymes in biological systems.

Brain, as the source of neural activities such as perceptions and emotions, consists of the dynamic and complex networks of neurons that implement brain functions through electrical and chemical interactions. Therefore, analyzing and monitoring neurochemicals in living brain can greatly contribute to uncovering the molecular mechanism in both physiological and pathological processes, and to taking a further step in developing precise medical diagnosis and treatment against brain diseases. Through collaborations across disciplines, a handful of analytical tools have been proven to be befitting in neurochemical measurement, spanning the level of vesicles, cells, and living brains. Among these, electrochemical methods endowed with high sensitivity and spatiotemporal resolution provide a promising way to precisely describe the dynamics of target neurochemicals during various neural activities. In this review, we expand the discussion on strategies to address two key issues of in vivo electrochemical sensing, namely, selectivity and biocompatibility, taking our latest studies as typical examples. We systematically elaborate for the first time the rationale behind engineering electrode/brain interface, as well as the unique advantages of potentiometric sensing methods. In particular, we highlight our recent progress on employing the as-prepared in vivo electrochemical sensors to unravel the molecular mechanism of ascorbate in physiological and pathological processes, aiming to draw a blueprint for the future development of in vivo electrochemical sensing of brain neurochemicals.