Wen-You Li

Photothermal therapy has attracted extensive attention in tumor treatment owing to its spatiotemporal controllability and noninvasiveness. However, the nonselective “always on” nature of traditional photothermal nanoagents together with the intrinsic thermal resistance within tumor cells has hampered the therapeutic efficacy. Herein, we developed a tumor-microenvironment-responsive transformable prenanotherapeutic platform with a polyethyleneimine (PEI)-coated tannic acid-Ca2+ chelate core and an outer shell of Fe2+-doped ZIF-90, which enabled the in situ generation of photothermal agents, synchronous activation of multiple therapeutic modalities, as well as cascaded synergistic enhancement of antitumor potency. First, degradation triggered by high-concentration adenosine triphosphate (ATP) and mild acidity within tumor cells liberated Fe2+ to catalyze hydroxyl radical (·OH) production for chemodynamic therapy. Meanwhile, the generated Fe3+ readily underwent in situ self-assembly with tannic acid to form photothermal agents, which competitively released Ca2+ and induced calcium overload. Subsequently, the dual mitochondrial destruction pathway induced by ·OH and excess Ca2+ suppressed ATP synthesis, which further downregulated the expression of heat shock protein 70 and elevated tumor cell thermosensitivity to realize mild photothermal therapy. Moreover, heat generated via photothermal agents enhanced the efficiency of Fenton-like reactions for robust ·OH accumulation, further improving the therapeutic efficacy. In vitro experiments revealed the underlying synergistic antitumor mechanism, while in vivo experiments confirmed the remarkable tumor suppression capacity of the nanomaterial. Notably, an intelligent TME-responsive “OFF-to-ON” multifunctional nanoplatform was fabricated on the basis of differential binding affinities of metal ions and polyphenols, offering a safer, more efficient and precise strategy for synergistic cancer therapy.

Copper ions (Cu2+) and nitrite (NO2−) are two prevalent pollutants in aquatic environments that frequently coexist and potentially exert synergistic toxic effects. However, the simultaneous and precise quantification of these two species remains a formidable challenge due to signal interference. In this study, a triple-emission lanthanide metal−organic framework (Ln-MOF) ratiometric fluorescent probe, Eu/Tb-BDC/BDC-NH2, was engineered via a dual-ligand and dual-lanthanide strategy. Under a single excitation wavelength (260 nm), the probe exhibits three independent and orthogonal emission signals at 433, 544, and 695 nm, originating from the BDC-NH2-related emission, Tb3+, and Eu3+, respectively. Unlike conventional sensors, Cu2+ and NO2− selectively quench the fluorescence at 433 and 544 nm (F433 and F544), respectively, while the 695 nm emission (F695) remains essentially stable as a reliable internal reference. By integrating two ratiometric sensing channels (F433/F695 and F544/F695), this platform enables the simultaneous detection of Cu2+ and NO2− within a single sensing system. The system demonstrates a rapid response (30 s), low detection limits, and reliable performance in practical water analysis. This work not only provides a novel paradigm for designing multi-emission Ln-MOFs but also offers new insights into the simultaneous analysis of multiple pollutants in complex environmental samples.

Nanozyme-mediated tumor chemodynamic therapy (CDT) is severely hampered by insufficient nanozyme catalytic efficiency within weakly acidic and redox-imbalanced tumor microenvironments (TMEs) and unsatisfactory tumor-targeting accumulation. Herein, we rationally constructed a Fe/Cu bimetallic metal-organic framework (MOF) nanozyme carrier, which was loaded with 3-amino-1,2,4-triazole (3-AT) and surface-functionalized with folic acid, denoted MOF(Fe-Cu)@3-AT-FA (FCAF), for self-sustained and high-efficiency CDT. The nanoplatform simultaneously realized multiway ROS cascade amplification, involving folate-mediated active targeting, bimetallic electron transfer for strengthened intrinsic nanozyme activity, catalase inhibition by 3-AT to sustain sufficient H2O2 substrates, and GSH exhaustion to attenuate intracellular antioxidant defense, serving as an all-in-one programmable nanoreactor. Benefiting from synergistic effects, FCAF achieved robust amplified CDT and remarkable oxidative stress damage. In vitro and in vivo results validated that FCAF markedly suppressed FRα-positive tumor proliferation with favorable biocompatibility. This study provided a universal cascade-amplification strategy for nanozyme-based CDT, laying novel perspectives for advanced nanotherapeutics.

Aerobic glycolysis fuels tumor proliferation, making it a critical target for tumor metabolic therapy. However, existing small-molecule inhibitors suffer from limitations like insufficient selectivity and systemic toxicity. In this study, a GSH-responsive molecularly imprinted polymer nanodelivery system (ML@MIP) was prepared for the precise delivery of the antimetabolite drug lonidamine (LND) and its synergistic treatment with CDT. ML@MIP employed LND-loaded metal-organic framework MOF-199 as the carrier and utilized the epitope of glucose transporter 1 (GLUT1) overexpressed on tumor cell membranes as the template. Through radical polymerization, an imprinted layer was constructed with specific recognition capabilities. Within the imprinted layer, GSH-sensitive disulfide bonds were introduced as crosslinking structural units into the imprinting network, endowing the material with controlled release properties triggered by the tumor microenvironment. ML@MIP actively recognized tumor cells with high GLUT1 expression. Upon entering the cell, high level GSH triggered disulfide bond cleavage in the imprinted layer and disassembly of the inner MOF-199 framework, enabling programmed drug release. The released LND inhibited hexokinase 2 (HK2) activity, which obstructed glycolysis pathways and further disrupted mitochondrial function. Concurrently, released Cu2+ was reduced by GSH to Cu+, which catalyzed the conversion of endogenous H2O2 into highly toxic hydroxyl radicals (·OH) through a Fenton-like reaction, thereby causing cellular damage. ML@MIP achieved high LND loading (78.2%) and a responsive release (66.6%). In vitro and in vivo experiments demonstrated that ML@MIP exhibited effective tumor targeting, significant antiproliferative effects, and good biocompatibility. This nanomaterial provides a novel, highly efficient nano-targeted delivery platform for precision synergistic cancer therapy.

Mitochondrion, a key subcellular organelle, acts as the cell's energy supplier and metabolic regulator. Given its vital functions and distinct thermal sensitivity, it's a suitable target for tumor photothermal therapy (PTT). However, current mitochondrial targeting agents are easily cleared during in vivo circulation and may non‐specifically target normal cells. Herein, to address these issues, a novel cascade‐targeting molecularly imprinted polymer (MIP) with charge‐reversal capability was constructed, avoiding exogenous ligand modification. During MIP synthesis, Fe ₃ O ₄ modified with (3‐carboxypropyl)triphenylphosphonium bromide was used as the carrier to provide photothermal effect and mitochondrial targeting. Furthermore, incorporating 2‐methacryloyloxyethyl phosphorylcholine boosted the imprinting factor and endowed charge reversal, enabling specific, stealthy tumor targeting and enhanced cellular internalization under weak acidity. Following intracellular entry, glutathione‐mediated degradation of the reductive cross‐linker released the carrier for second‐stage mitochondrial targeting. Thereafter, under 808 nm laser irradiation, Fe ₃ O ₄ exerted a robust photothermal effect. Cellular uptake and mitochondrial colocalization confirmed cascade targeting capability, while in vitro tumor spheroid penetration demonstrated charge‐reversal MIP facilitated more efficient internalization. In vivo experiments revealed MIP exhibited the strongest anti‐tumor efficacy under irradiation. This work fully leveraged the designability of MIP, integrating charge reversal with cascade targeting functionalities, and provided a novel strategy for improving PTT.

Mechanisms underlying NPY@ZIF-RG synergistic pharmacotherapy for epilepsy.

In this work, a dual-emission material based on lanthanide metals was synthesized and used as a ratio fluorescence sensor to respond to Hg²⁺ and H₂O₂, respectively. Tb-BDC-NH₂ as a bimetal MOFs had double ligands and exhibited double fluorescence emission peaks at 550 nm and 450 nm. The two emission peaks of Tb-BDC-NH₂ can be quenched by Hg²⁺ and H₂O₂ respectively, forming a built-in calibration signal for ratio fluorescence detection. Based on the different detection conditions of the Hg²⁺ and H₂O₂, the simultaneous detection of the two detection substances can be achieved with simple operation. This detection system had good stability and anti-interference ability. Under optimal conditions, the detection limit for Hg²⁺ detection was 0.2 µM. Meanwhile, for the detection of H₂O₂, the detection limit was 11 µM and large linear ranges were obtained. Through actual sample testing, it had been proven that the ratio fluorescence sensor based on Tb-BDC-NH₂ had good application prospects. And the work also provided a new idea for double substances detection.