Tianxiang Chen

Precise identification and quantitative analysis of the functional boundary are essential for accurate diagnosis and treatment. This not only relates to the precise delineation of lesion areas but also holds significant scientific importance for revealing tumor formation, progression, invasion, and metastasis across the functional boundary. The complex tumor microenvironment and variable biological characteristics present unprecedented opportunities and challenges for precise identification and quantification of the functional boundary. Unlike conventional magnetic resonance imaging (MRI) probes, responsive organic MRI probes rely on local tumor stimuli to trigger covalent bond cleavage, aggregation/disaggregation, conformational rearrangement, electronic state transitions, exchange rate changes, radical/nonradical interconversions, etc., ultimately translating into measurable MR readout signals. This provides a novel technical pathway for the precise determination and quantitative analysis of functional boundaries. In recent years, focusing on features such as pH decrease, protease overexpression, elevated levels of reactive oxygen species (ROS), and hypoxia, responsive organic MRI probes have gradually formed a relatively systematic research framework. This review follows a clear route from microenvironmental abnormality to responsive site, stimulus-triggered event, and MR readout, systematically reviewing the design principles and response mechanisms of responsive sites under different stimulus types. It points out that the key challenge facing current imaging probes is not the continuous addition of functions but establishing clearer, more quantifiable, and biologically interpretable imaging strategies, providing theoretical support and research ideas for achieving a precise determination and quantitative analysis of the functional boundary.

A major challenge in biofilm-associated infection therapy is overcoming biofilm barriers while eradicating embedded bacteria without inducing antibiotic resistance. Here, we report an antibiotic-free microbotic platform that synergistically integrates magnetomechanical biofilm disruption with localized nanozyme-mediated bactericidal activity, enabling efficient and biocompatible biofilm eradication in vivo. Under a rotating magnetic field, nanozyme microbots transition from individual spinning to reconfigurable vortex swarming, generating strong local fluid shear forces that mechanically disrupt the extracellular polymeric substance matrix and drive deep penetration into biofilms. Within the disrupted biofilm, the Fe₃O₄ nanozyme cores catalyze endogenous H₂O₂ to produce bactericidal hydroxyl radicals, resulting in effective elimination of both Gram-positive and Gram-negative bacteria. In murine biofilm infection models, the nanozyme microbots significantly reduce the bacterial burden, accelerate wound closure, suppress inflammation, and promote angiogenesis. This work establishes a mechanochemical microbotic strategy that combines programmable swarm dynamics with nanozyme catalysis, providing a promising antibiotic-independent approach to treating chronic biofilm-associated infections.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Its pathogenesis involves aberrant activation and aggressive proliferation of fibroblast-like synoviocytes (FLS), excessive macrophage infiltration, and disrupted M1/M2 macrophage polarization within the synovial microenvironment (SME). However, current therapies remain inadequate for precise SME modulation, often leading to limited efficacy and poor prognosis. To address this challenge, we developed a multifunctional nanocapsule, termed RP/HP@Mn/L, which is composed of a low molecular weight heparin (LMWH)-modified, Mn²⁺-doped hollow mesoporous polydopamine (HP) nanocarrier co-loaded with rapamycin (Rap) and paeoniflorin (Pae). This nanocapsule's dual-ligand strategy targets P-selectin on inflamed endothelial cells and integrin αM on inflammatory macrophages, enabling precise spatiotemporal accumulation at the pathological site. This nanocapsule enables spatiotemporally specific targeting of both inflammatory endothelial cells and inflammatory macrophages, thereby enhancing precise drug delivery to pathological sites. Mechanistic investigations revealed that RP/HP@Mn/L, in combination with mild photothermal therapy (PTT) mediated by HP, effectively suppressed FLS proliferation and invasion. Concurrently, it promoted the polarization of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. These synergistic effects facilitated the remodeling of the SME, thereby alleviating synovitis and enhancing bone repair in RA. In conclusion, this study proposes a spatiotemporally targeted combinatorial nanotherapeutic strategy that integrates multimodal mechanisms for SME modulation. This approach represents a promising therapeutic platform for improving outcomes in RA and other autoimmune disorders.

Oxidative stress (OS) serves as a fundamental pathological component in a multitude of chronic diseases, necessitating an all‐round theranostic strategy for simultaneous precision intervention and real‐time monitoring. Cerium‐based nanomaterials (CeNMs), particularly cerium oxide nanoparticles (CeNPs), offer a disruptive theranostic platform on account of their unique Ce ³⁺ /Ce ⁴⁺ redox cycling, intrinsic superoxide dismutase (SOD)‐ and Catalase (CAT)‐mimetic activities, responsiveness to pathological microenvironments (e.g., high ROS and low pH), and inherent or engineerable imaging capabilities (e.g., CT contrast and fluorescence). This review not only systematically probes deep into four “diagnosis‐therapy” bridging mechanisms of CeNMs in oxidative‐stress‐correlated diseases, but also digs into how these mechanisms effectively address the limitations of conventional strategies. On that account, we explore the integrated potential of CeNMs in antioxidant therapy and dynamic monitoring. These materials are poised to become a critical engine driving precision medicine in oxidative‐stress‐related disorders. For this reason, it facilitates interventions characterized by more individualized, dynamically regulated and safely controllable design.

Early diagnosis of liver diseases has long faced serious challenges such as insufficient sensitivity, low specificity and difficulty in revealing molecular lesion information by conventional imaging methods. With the rapid development of nanoscience, nanomolecular probes exhibit tuneable structure, modifiable surface and excellent biocompatibility, and their responsive properties have gradually become an ideal medium for connecting molecular pathological changes and image visualisation. This review reveals that functionalised nanoprobes responsive to disease microenvironment‐specific signals (e.g., reactive oxygen species, enzymes, pH, metal ions, etc.) can enable the visualisation and tracking of molecular events in liver diseases, thereby promoting the shift of diagnostic paradigm from traditional morphological assessment to precise identification at the functional and molecular levels. This article not only systematically reviews the latest application progress of responsive nanoprobes in liver disease diagnosis, but also demonstrates their great potential to shift the diagnostic paradigm from macro‐anatomy to micro‐molecule. At the same time, this article presents an in‐depth analysis of the key bottlenecks in the clinical translation process, thereby outlining directions for the rational design of next‐generation intelligent nano‐diagnostic tools. Collectively, this work offers new insights and strategies to accelerate the early and precise diagnosis and treatment of liver diseases.

Despite the critical role of succinylation as a posttranslational modification in regulating cellular homeostasis and metabolic pathways, achieving precise control over mitochondrial function and homeostasis to induce apoptosis in breast cancer remains a significant challenge. In this study, we designed a succinylated D-type neuropeptide integrated with an iron-based probe aimed at regulating mitochondrial function and homeostasis through SIRT5-mediated desuccinylation. The probe is selectively delivered to breast cancer cells via Y₁ receptor-mediated endocytosis, where it undergoes SIRT5-catalyzed desuccinylation within the mitochondria. This enzymatic modification induces substantial changes in the secondary structure of the D-type neuropeptide, transforming the probe into aggregates that disrupt the mitochondrial membrane potential and electron transport. By interacting competitively with cellular desuccinylation pathways, this probe further disturbs cellular homeostasis, ultimately leading to apoptosis in tumor cells. Additionally, we observe the upregulation of key genes associated with inflammation and ferroptosis, which may contribute to the establishment of an inflammatory microenvironment, thereby enhancing the antitumor effect. Notably, the aggregation process shifts the magnetic resonance imaging (MRI) contrast from T₁ to T₂, enabling the real-time visualization of mitochondrial perturbations. This work establishes a versatile platform for designing neuropeptide-based nanoprobes with diagnostic and therapeutic potential for the treatment of breast cancer.

Serous effusions, including pleural effusion and ascites, commonly occur in advanced cancers like lung and ovarian carcinomas. Detecting tumor cells in these effusions is crucial for assessing cancer metastasis. However, clinical methods mainly include cytological examination, which has limited sensitivity, and complex cell block technology that requires large volumes of serous effusion. Surface-enhanced Raman spectroscopy (SERS), with its high sensitivity and noninvasive nature, has emerged as a crucial tool for liquid biopsies. Building on this technology, a novel SERS bioprobe was specifically designed for the precise identification and capture of tumor cells in serous effusions, utilizing a composite material. The SERS bioprobes offer strong SERS enhancement, excellent spectral reproducibility, and molecular targeting, thereby enhancing detection specificity. Furthermore, SERS classification models were established to categorize samples based on tumor cell concentrations in serous effusions, enabling semiquantitative diagnostic capability. Notably, machine learning-assisted analysis enables rapid processing and classification of numerous Raman spectra and thorough feature extraction and greatly improves the SERS bioprobe's diagnostic accuracy. Consequently, the combination of SERS bioprobes and machine learning provides a rapid and effective detection method that overcomes the low sensitivity of conventional cytological detection in serous effusions and enables assessment of tumor cell concentration ranges within these fluids.

The renal tubule (RT) is one of the primary sites of origin and the most important sites of occurrence of renal injury, renal fibrosis (RF) and renal cell carcinoma (RCC). Given the complex pathogenesis of these conditions and the unique anatomical structure of the kidney, traditional diagnostic methods such as liquid biopsy, tissue biopsy, and conventional imaging have significant obstacles in achieving early and accurate diagnosis. Nanoprobes have unique physicochemical properties of high specificity and high sensitivity, and can accurately change the pathological changes in the kidney into distinguishable signal differences in the image, which can effectively overcome the technical bottleneck in the early diagnosis of renal tubular diseases. This article systematically reviews the progress in the development of nanoprobes in the diagnosis of renal tubular diseases, emphasizes on the analysis of the design, functional modification and targeting strategies of molecular probes, compares the advantages and disadvantages of various modification and targeting strategies, and organizes the technical context based on preclinical research data. It seeks to open viable routes to the clinical translation of nanoprobes, development directions for multimodal/microenvironment‐responsive diagnostic platforms and provide key technical support to upgrade the personalized diagnosis of renal tubular diseases.