Targeted protein degradation (TPD) technologies have emerged as a powerful strategy for eliminating disease-causing proteins by hijacking endogenous degradation systems. Over the past decade, multiple TPD modalities—such as proteolysis-targeting chimeras (PROTACs), molecular glues, lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), and others—have been developed to engage distinct cellular degradation pathways including the proteasome and lysosome systems. Despite their therapeutic promise, current TPD agents still face challenges of poor solubility, limited bioavailability, and inefficient delivery. To address these barriers, this review highlights the integration of nanotechnology with TPD as a promising approach. We summarize recent progress in proteasome- and lysosome-directed TPD strategies and describe how nanomaterials—including liposomes, polymers, inorganic nanoparticles, carbon dots, and ferritin—are applied to construct multivalent degraders, enhance pharmacokinetics, and demonstrate synergistic efficacy when combined with chemotherapy, immunotherapy, or catalytic therapies. In addition, we discuss the emerging convergence of nanozymes with TPD, where catalytic generation of reactive oxygen species not only regulates ubiquitination–deubiquitination balance but also facilitates endosomal disruption and boosts therapeutic efficacy. By bridging mechanistic innovation with nano-enabled platforms, nano-based TPD technologies offer enhanced precision, safety, and multifunctionality. Their continued advancement is poised to accelerate clinical translation and reshape strategies for treating complex and previously intractable diseases.

Cisplatin resistance in tumors is closely linked to the upregulation of the nucleotide excision repair (NER) pathway, particularly the excision repair cross-complementing-1–xeroderma pigmentosum complementation group F (ERCC1–XPF) complex. Here, we present a tumor-responsive microneedle (MN) patch platform for localized co-delivery of a NER-targeting proteolysis-targeting chimera (PROTAC) degrader (NERiP) and a Pt(IV) prodrug to overcome this resistance. This platform integrates pH-responsive PEG-PAE micelles, which co-encapsulate NERiP and Pt(IV), into dissolvable methacrylated hyaluronic acid microneedles for transdermal administration. Upon insertion into tumor-bearing skin, the MNs enable sustained and localized release of the micelles. In the mildly acidic tumor microenvironment, the micelles undergo surface charge reversal and rapid disassembly, resulting in synchronized release of both agents. This spatiotemporally coordinated delivery effectively downregulates ERCC1–XPF proteins and promotes platinum-induced DNA crosslinking, thereby enhancing apoptosis in cisplatin-resistant A375/CDDP melanoma cells. In vivo studies demonstrate that MN-mediated delivery significantly improves intratumoral drug accumulation and deep tissue penetration, achieving a tumor growth inhibition rate of 79.9% with minimal systemic toxicity. By combining tumor microenvironment-responsive release with minimally invasive localized delivery, this strategy enables synergistic NER pathway suppression and platinum-mediated genotoxicity. Furthermore, the MN platform ensures deep intratumoral distribution and prolonged retention, offering a promising therapeutic approach to address platinum resistance in solid tumors.

During criminal case investigations, blood evidence tracing is critical for criminal investigation. However, the blood stains are often cleaned or covered up after the crime, resulting in trace residue and difficult tracking. Therefore, a highly sensitive and specific method for the rapid detection of human blood stains remains urgent. To solve this problem, we established a nanozyme-based strip for rapid detection of blood evidence with high sensitivity and specificity. To construct reliable nanozyme strips, we synthesized CoFe₂O₄ nanozymes with high peroxidase-like activity by scaling up to gram level, which can be supplied for six million tests, and conjugated antibody as a detection probe in nanozyme strip. The developed CoFe₂O₄ nanozyme strip can detect human hemoglobin (HGB) at a concentration as low as 1 ng/mL, which is 100 times lower than the commercially available colloidal gold strips (100 ng/mL). Moreover, this CoFe₂O₄ nanozyme strip showed high generality on 12 substrates and high specificity to human HGB among 13 animal blood samples. Finally, we applied the developed CoFe₂O₄ nanozyme strip to successfully detect blood stains in three real cases, where the current commercial colloidal gold strip failed to do. The results suggest that the CoFe₂O₄ nanozyme strip can be used as an effective on-scene detection method for human blood stains, and can further be used as a long-term preserved material evidence for traceability inquiry.

The correlation between Epstein-Barr virus (EBV) infection and nasopharyngeal carcinoma (NPC) risk has been extensively researched. The continual monitoring of EBV-IgAs provides a promising approach of NPC screening in its early stage. In this study, we successfully synthesized a single-atom nanozyme (SANzyme) through the application of iron-porphyrin based metal organic framework (MOF-FeP). The MOF-FeP possesses precisely-defined electronic and geometric structures that accurately mimic highly-evolved catalytic site of natural peroxidase. The peroxidase-like activity of MOF-FeP enables it to catalyze the chemiluminescence of luminol substrate. By integrating MOF-FeP into a traditional strip, we created a rapid and highly-sensitive evaluation tool for detecting EBV-IgAs. Importantly, the MOF-FeP strip enables the simultaneous detection of three EBV-IgAs, greatly improving the accuracy of EBV-associated NPC screening. The sensitivities of the MOF-FeP strip (75.56%–93.30%) surpass those of current enzyme-linked immunosorbent assay (ELISA) methods (64.44%–82.22%). This test takes only 16 min to perform as opposed to the customary 1–2 h required for standard ELISA. Additionally, the MOF-FeP strip is suitable for whole blood samples, thereby significantly simplifying the sample preparation and detection process. In conclusion, the MOF-FeP strip combines the simplicity of traditional strip with the high catalytic activity of SANzyme. Our innovative MOF-FeP strip offers a new point-of-care strategy for EBV-IgAs detection, which is expected to markedly facilitate early screening for EBV-associated diseases.

Nanozymes are nanomaterials with enzyme-like properties that have attracted significant interest owing to their high stability, easy preparation, and tunable catalytic properties, especially in the field of cancer therapy. However, the unfavorable catalytic effects of nanozymes in the acidic tumor microenvironment have limited their applications. Herein, we developed a biomimetic erythrocyte membrane-camouflaged ultrasmall black phosphorus quantum dots (BPQDs) nanozymes that simultaneously exhibited an exceptional near-infrared (NIR) photothermal property and dramatically photothermal-enhanced glucose oxidase (GOx)-like activity in the acidic tumor microenvironment. We demonstrated the engineered BPQDs gave a photothermal conversion efficiency of 28.9% that could rapidly heat the tumor up to 50 ℃ while effectively localized into tumors via homing peptide iRGD leading after intravenously injection. Meanwhile, the significantly enhanced GOx-like activity of BPQDs under NIR irradiation was capable of catalytical generating massive toxic reactive oxygen species via using cellular glucose. By combining the intrinsic photothermal property and the unique photothermal-enhanced GOx-like catalytic activity, the developed BPQDs were demonstrated to be an effective therapeutic strategy for inhibiting tumor growth in vivo. We believe that this work will provide a novel perspective for the development of nanozymes in tumor catalytic therapy.

Nanozymes are nanomaterials with enzyme-like properties that have attracted significant interest owing to their capability to address the limitations of traditional enzymes such as fragility, high cost, and impossible mass production. Over the past decade, a broad variety of nanomaterials have been found to mimic the enzyme-like activity by engineering the active centers of natural enzymes or developing multivalent elements within nanostructures. Carbon nanomaterials with well-defined electronic and geometric structures have served as favorable surrogates of traditional enzymes by mimicking the highly evolved catalytic center of natural enzymes. In particular, by combining the unique electronic, optical, thermal, and mechanical properties, carbon nanomaterials-based nanozymes can offer a variety of multifunctional platforms for biomedical applications. In this review, we will introduce the enzymatic characteristics and recent advances of carbon nanozymes, and summarize their significant applications in biomedicine.

Artificial nanorobot is a type of robots designed for executing complex tasks at nanoscale. The nanorobot system is typically consisted of four systems, including logic control, driving, sensing and functioning. Considering the subtle structure and complex functionality of nanorobot, the manufacture of nanorobots requires designable, controllable and multi-functional nanomaterials. Here, we propose that nanozyme is a promising candidate for fabricating nanorobots due to its unique properties, including flexible designs, controllable enzyme-like activities, and nano-sized physicochemical characters. Nanozymes may participate in one system or even combine several systems of nanorobots. In this review, we summarize the advances on nanozyme-based systems for fabricating nanorobots, and prospect the future directions of nanozyme for constructing nanorobots. We hope that the unique properties of nanozymes will provide novel ideas for designing and fabricating nanorobotics.

Atherosclerotic plaque rupture results in thrombus formation and vessel occlusion, and is the leading cause of death worldwide. There is a pressing need to identify plaque vulnerability for the treatment of carotid and coronary artery diseases. Nanomaterials with enzyme-like properties have attracted significant interest by providing biological, diagnostic and prognostic information about the diseases. Here we showed that bioengineered magnetoferritin nanoparticles (M-HFn NPs) functionally mimic peroxidase enzyme and can intrinsically recognize plaque-infiltrated active macrophages, which drive atherosclerotic plaque progression and rupture and are significantly associated with the plaque vulnerability. The M-HFn nanozymes catalyze the oxidation of colorimetric substrates to give a color reaction that visualizes the recognized active macrophages for one-step pathological identification of plaque vulnerability. We examined 50 carotid endarterectomy specimens from patients with symptomatic carotid disease and demonstrated that the M-HFn nanozymes could distinguish active macrophage infiltration in ruptured and high-risk plaque tissues, and M-HFn staining displayed a significant correlation with plaque vulnerability (r = 0.89, P < 0.0001).