Jianlin Shi

Bladder cancer is a type of prevalent malignant tumor of the urinary system, for which transurethral endoscopic resection serves as the first-line clinical treatment, followed by adjuvant intravesical chemotherapy or BCG immunotherapy. Current clinical regimens suffer largely from surgical trauma, procedural risks, long treatment cycles, severe systemic side effects, and high recurrence rates; conventional tumor cell-killing modalities relying on highly toxic chemotherapeutics and vaccines will inevitably damage normal tissues and induce less-tolerable adverse reactions in patients. By overturning this conventional therapeutic philosophy, we previously proposed a globally pioneering bladder cancer disaggregation therapy: calcium chelation disrupts intercellular cadherin-mediated adhesion, triggering exfoliation and detachment of tumor cells, which are subsequently excreted from the body via urine. Taking advantage of the unique anatomical and physiological characteristics of the bladder, this strategy achieves noninvasive tumor elimination through spontaneous urinary expulsion. To further enhance the disaggregation efficiency, the present work advances this concept by incorporating collagenase to realize the dual disruption of both cadherin and collagen proteins. To this end, we constructed a layered double hydroxide (LDH) nanoplatform coloaded with collagenase and EDTA. The nanosystem efficiently degrades key extracellular matrix components, thereby relieving steric hindrance and exposing cellular surfaces, which significantly promotes the subsequent disruption of intercellular junctions via enhanced EDTA accessibility for calcium deprivation from E-cadherin. This work establishes an efficient, noncell-killing modality for the physical clearance of bladder tumors, offering a promising alternative clinical strategy to suppress tumor recurrence and reduce systemic toxic side effects.

The performance of proton exchange membrane fuel cells (PEMFCs) is critically governed by the cathodic triple-phase interface, where platinum catalyst poisoning and inefficient proton/oxygen transport severely impede the oxygen reduction reaction. Inspired by the selective transport of biological membranes, we herein develop a porphyrin-based organic network (H-PorBz) as a multifunctional ionomer modifier to reconfigure the catalyst/ionomer/gas triple-phase interface. In situ noncovalent cross-linking between the H-PorBz and Nafion via NH+-H···SO3– interactions forms an interfacial layer that decouples proton and oxygen transport while suppressing sulfonate-induced Pt poisoning. Spectroscopic and computational studies reveal that H-PorBz simultaneously enhances proton conduction and oxygen transport by establishing a low-barrier proton-transfer network and tuning nanopore polarity. This membrane-mimetic design reduces sulfonate coverage on Pt by 28% and oxygen-transport resistance by 39.4%, delivering a mass-specific power density of 15.8 W mgPt–1 under H2/air conditions, 1.7-fold that of a conventional Pt/C@Nafion cathode. The composite ionomer also demonstrates excellent durability (>120 h at 0.6 V), with a voltage decay rate below 50 μV h–1. This work presents a bioinspired interfacial engineering strategy that reconfigures the three-phase region to mitigate catalyst poisoning and transport losses, offering a viable route to high-performance low-Pt PEMFCs.

Abnormal metabolic reprogramming is a recognized hallmark of cancer, yet the clinical translation of cancer metabolic therapy (CMT) by conventional chemo‐drugs remains a great challenge due to their poor drug targetability, short circulation time, and low bioavailability. Nanomedicines, owing to their great feasibility in rational designs, facile fabrication, and excellent biocompatibility, offer a powerful platform to overcome the drawbacks of current clinical drugs and enable precise modulation of cancer metabolism. In this review, we provide a critical overview of recent advances in nanomedicine‐based CMT. We first summarize the reprogrammed metabolic landscape of cancer cells and the metabolic crosstalk within the tumor microenvironment. Then, nanomedicine strategies targeting glucose, lipid, amino acid, nucleotide, and carboxylic acid metabolism are summarized and discussed in a comprehensive way, with an emphasis on nanomaterial design principles and regulatory mechanisms. Finally, key challenges and future prospects for clinical translation are discussed, aiming to establish nanomedicine‐enabled CMT as a next‐generation paradigm for effective and safe cancer treatment.

Though playing a critical role, the controllable and directional migration of reactive species in chemical reactions is still hard to achieve. Here, we propose an interfacial engineering strategy for constructing a hydrogen spillover nanodiode that channels hydrogen unidirectionally. Such a nanodiode design is materialized in a composite WO _x /TiO ₂ /Pt catalyst with spatially separated structure, where WO _x and Pt particles are dispersed on the outer and inner surfaces of porous TiO ₂ nanotubes, respectively. This nanodevice permits forward H migration (Pt→TiO ₂ →WO _x ) while suppresses the reverse path (WO _x →TiO ₂ ), as directly evidenced by in situ x‐ray absorption fine structure characterization under hydrogenation and H ₂ generation reactions. This rectification behavior originates from the diode characteristics of the TiO ₂ –WO _x heterojunction, which hinders both proton and electron transfer from WO _x to TiO ₂ . Consequently, WO _x /TiO ₂ /Pt accumulates highly concentrated Brønsted acid sites in H ₂ atmosphere and thus exhibits superior catalytic performance compared to the closely contacted WO _x –Pt/TiO ₂ catalyst. Up to 5.3 times higher liquid alkane yield has been achieved over WO _x /TiO ₂ /Pt relative to WO _x –Pt/TiO ₂ in the polyethylene hydrocracking reaction. This nanodiode design strategy is general and can be extended to other catalysts/species, offering mechanistic insight and boosting catalytic performance in diverse reactions.

Though playing a critical role, the controllable and directional migration of reactive species in chemical reactions is still hard to achieve. Here, we propose an interfacial engineering strategy for constructing a hydrogen spillover nanodiode that channels hydrogen unidirectionally. Such a nanodiode design is materialized in a composite WO _x /TiO ₂ /Pt catalyst with spatially separated structure, where WO _x and Pt particles are dispersed on the outer and inner surfaces of porous TiO ₂ nanotubes, respectively. This nanodevice permits forward H migration (Pt→TiO ₂ →WO _x ) while suppresses the reverse path (WO _x →TiO ₂ ), as directly evidenced by in situ x‐ray absorption fine structure characterization under hydrogenation and H ₂ generation reactions. This rectification behavior originates from the diode characteristics of the TiO ₂ –WO _x heterojunction, which hinders both proton and electron transfer from WO _x to TiO ₂ . Consequently, WO _x /TiO ₂ /Pt accumulates highly concentrated Brønsted acid sites in H ₂ atmosphere and thus exhibits superior catalytic performance compared to the closely contacted WO _x –Pt/TiO ₂ catalyst. Up to 5.3 times higher liquid alkane yield has been achieved over WO _x /TiO ₂ /Pt relative to WO _x –Pt/TiO ₂ in the polyethylene hydrocracking reaction. This nanodiode design strategy is general and can be extended to other catalysts/species, offering mechanistic insight and boosting catalytic performance in diverse reactions.

Acting as frontline sensors during cardiovascular injury, endothelial cells respond to acute ischemia by releasing exosomes as angiocrine signals for intercellular communication and cardioprotection. However, these endogenous signals are poorly utilized because released exosomes distribute systemically and show limited exposure in injured myocardium. Here we develop a systemically administered nanosystem for relocalizing circulating endothelial exosomes towards the myocardium, increasing their local availability. The nanosystem captures circulating endothelial exosomes, mediates their transvascular relocalization and promotes delivery to cardiomyocytes in the ischemic myocardium, thereby enhancing the local availability of native angiocrine signals. In a murine model of acute cardiac ischemia using male mice, this strategy increases endothelial exosome exposure in myocardium, improves cardiomyocyte survival, and preserves cardiac function. This approach enhances the reception of native angiocrine signals at the injured myocardium, therefore converting the originally diffuse, short-lived response into a sustained, organ-specific therapeutic exposure.

The luminal androgen receptor (LAR) subtype of triple‐negative breast cancer (TNBC) represents a formidable therapeutic challenge, necessitating sophisticated strategies that exploit unique tumor vulnerabilities. In the present work, we introduce a biomimetic nanotherapeutic that integrates single‐atom iron nanocatalysts (FeSA) co‐loaded with a CRISPR‐Cas9 plasmid targeting Glutathione Peroxidase 4 ( Gpx4 ), the key regulator of ferroptosis, and is camouflaged with a homologous cancer cell membrane to ensure precise tumor tropism and excellent biocompatibility. In an orthotopic LAR‐TNBC model, the nanotherapeutic achieved ∼98% tumor regression and markedly extended survival. Comprehensive mechanistic analyses confirmed efficient on‐target Gpx4 disruption, which synergistically amplified the FeSA‐catalyzed ferroptotic cascade. Unbiased transcriptomic profiling further revealed extensive reprogramming of the tumor molecular landscape, resulting in significant cancer cell ferroptosis by DNA damage response and p53 signaling pathway activation. This work establishes a highly synergistic and targeted approach, presenting a potent therapeutic modality for aggressive and chemoresistant malignancies.

Pulmonary arterial hypertension (PAH) is a serious circulatory system disease characterized by redox imbalance, which results from the overexpressed reactive oxygen species (ROS) and inactivated antioxidation defense system. In this work, a dynamic chemical reconstruction strategy has been developed for PAH treatment through the in situ synthesis of antioxidant nanocatalyst MoO _y and selenium oxyanions from a molybdenum selenide nanosystem in response to the oxidative microenvironment of PAH. MoO _y nanoparticles catalyze the exogenous antioxidation reactions to scavenge ROS efficiently, while the soluble selenium oxyanions upregulate the expression of selenoproteins to reinforce the endogenous antioxidant defense system. These two processes cooperatively alleviate oxidative stress of pulmonary artery smooth muscle cells (PASMCs), thus suppressing their malignant proliferation/migration and finally mitigating pulmonary arterial remodeling for PAH treatment. This work presents a dynamic chemical reconstruction strategy for in situ synthesis of exogenous and endogenous antioxidants, offering a dual‐axis antioxidation approach for the treatment of multiple redox imbalance‐associated diseases.

Pulmonary arterial hypertension (PAH) is a serious circulatory system disease characterized by redox imbalance, which results from the overexpressed reactive oxygen species (ROS) and inactivated antioxidation defense system. In this work, a dynamic chemical reconstruction strategy has been developed for PAH treatment through the in situ synthesis of antioxidant nanocatalyst MoO _y and selenium oxyanions from a molybdenum selenide nanosystem in response to the oxidative microenvironment of PAH. MoO _y nanoparticles catalyze the exogenous antioxidation reactions to scavenge ROS efficiently, while the soluble selenium oxyanions upregulate the expression of selenoproteins to reinforce the endogenous antioxidant defense system. These two processes cooperatively alleviate oxidative stress of pulmonary artery smooth muscle cells (PASMCs), thus suppressing their malignant proliferation/migration and finally mitigating pulmonary arterial remodeling for PAH treatment. This work presents a dynamic chemical reconstruction strategy for in situ synthesis of exogenous and endogenous antioxidants, offering a dual‐axis antioxidation approach for the treatment of multiple redox imbalance‐associated diseases.