Qian He

This review systematically summarizes recent advances in oral nanozyme delivery systems, highlighting design strategies that overcome gastrointestinal barriers for targeted treatment of ROS-related inflammatory diseases.

Targeted delivery of protein therapeutics remains challenging for translating biologics into effective treatments. Here, we introduce a universal strategy leveraging elevated glycolysis, a hallmark of many pathological states, and its resulting extracellular acidification as a navigational cue. Therapeutic proteins are encapsulated within pH-responsive polymer shells that remain near-neutral at physiological pH but gradually gain positive charge under acidic conditions. This dynamic charge modulation allows nanocapsules to sense pH gradients between healthy and diseased tissues, directing them toward pathological sites. Unlike receptor-mediated targeting that operates over nanometer scales, this receptor-independent approach enables long-range targeting. In vivo models of cancer, chronic inflammation, and acute injury demonstrate selective accumulation of encapsulated proteins at diseased sites, enhancing therapeutic efficacy while reducing systemic toxicity. By transforming a ubiquitous metabolic signature into a directional driving force, this lactate acid gradient–mediated targeting (LaGET) platform offers a previously underexplored paradigm for targeted delivery of protein therapeutics.

As an emerging carbon-based nanomaterial, carbon dots (CDs) exhibit broad prospects in antimicrobial therapy owing to their unique physicochemical properties, excellent biocompatibility, and tunable multifunctional characteristics. This review systematically summarizes recent advances in the research on CDs in the antimicrobial field, including innovative construction strategies, mechanisms of action, theranostic applications, and safety evaluation. Regarding construction strategies, it highlights the design principles and antimicrobial properties of bio-derived CDs, drug molecule-directed CDs, charge-engineered CDs, metal-synergistic catalytic CDs, and amino acid-functionalized CDs. For mechanisms of action, it elaborates on the multi-target antimicrobial modes of CDs, such as physical disruption, oxidative stress induction, and metabolic interference. In terms of theranostic applications, it summarizes the innovative uses of CDs in photodynamic therapy, photothermal-photodynamic synergistic therapy, and tissue repair. Finally, it delves into safety concerns including the impacts of CDs on intestinal health, risks of metal doping, and environmental degradation behaviors. This review aims to provide theoretical guidance for the development of highly effective and safe antimicrobial CDs, while prospecting the challenges and opportunities in their clinical translation.

Nanozymes are a class of nanomaterial-based catalysts with enzyme-like functionalities. They exhibit excellent physicochemical properties and stable catalytic activity in both in vivo and in vitro environments, demonstrating immense potential for biomedical applications. Autoimmune diseases arise from the immune system’s erroneous attack on self-tissues or cells, affecting individuals across all age groups. Current therapies primarily rely on immunosuppressive drugs, which may control disease progression or alleviate symptoms but often fail to achieve a cure. Long-term use of these drugs is associated with significant side effects, imposing substantial health burdens on patients. Oxidative stress, driven by excessive reactive oxygen species (ROS) production or dysfunctional antioxidant defense systems, is a key mechanism underlying many autoimmune diseases. Excessive ROS accumulation exacerbates cellular damage and inflammatory responses, accelerating disease progression. Nanozymes, with their enzyme-mimicking catalytic capabilities, are ideal tools for modulating ROS levels, offering promising applications in the prevention and treatment of autoimmune diseases. Furthermore, by regulating the ROS microenvironment, nanozymes may enhance the proliferation, differentiation, and regenerative capacity of stem cells, further amplifying their therapeutic potential. This review comprehensively explores recent advancements in nanozymes for biomedical applications, focusing on their roles in oxidative stress modulation and mesenchymal stem cell (MSC)-based therapies. It aims to provide innovative insights and solutions for future clinical strategies.

Fluorescent carbon dots (CDs) represent a promising class of carbon nanomaterials exhibiting excellent optical stability, minimal toxicity, outstanding biocompatibility, and facile surface modification, rendering them ideal for diverse biomedical applications. However, designing CDs with efficient targeting capabilities for precise delivery to disease sites remains a significant challenge. This review provides an overview of recent advancements in the design strategies for targeted CDs, focusing on methods for achieving specific and accurate accumulation in tissues, organs, cells, organelles, and biomolecules. The versatile surface chemistry of CDs, including functional groups and carbon sites, facilitates the development of diverse structures, enabling active targeting through surface modification with targeting ligands, retention of targeting moieties, or utilization of endogenous proteins for targeting purposes. These strategies enhance the specificity and efficacy of CDs for both diagnostic and therapeutic applications, thereby advancing their potential for precise medical interventions. This review provides a comprehensive perspective on elucidating the structure-performance relationship of targeted CDs. Furthermore, the rational construction strategies offer valuable guidance for advancing the development of targeted nanomedicines and their biomedical applications.

Bimetallic/multimetallic nanozymes harness synergistic catalysis for advanced therapeutic, diagnostic, and environmental health applications.

Nanocarrier-mediated multi-level precision delivery overcomes biological barriers and enables stimuli-responsive targeting at the cellular and subcellular levels, offering transformative therapeutic potential for autoimmune diseases.

By mimicking enzymatic activities, nanozymes emerge as versatile platforms to reprogram immune responses, paving the way for next-generation immunotherapy.

Rational design of carbon dots through heteroatom doping and functional precursor selection for multifunctional enzyme-mimicking nanotherapeutics in oxidative stress-related diseases.