Engineered bacteria hold promise for remodeling immunosuppressive tumor microenvironments through innate immunogenicity and localized therapeutic delivery. While bacterial-derived metabolites are increasingly recognized as key mediators, their specific roles in interkingdom crosstalk remain underexplored. Here, we develop a programmable probiotic platform leveraging Lactobacillus gasseri (LG)-tumor metabolic interplay to potentiate bladder cancer therapy. The selected LG strain demonstrates superior tumor-colonizing ability and intrinsic H2O2/lactate biosynthesis, creating an optimal tumor microenvironment for hemoglobin-modified MnOx nanoparticles to enhance chemodynamic therapy efficacy. Mechanistically, microbial metabolites, including L-leucine, orchestrate neutrophil phenotypic reprogramming by suppressing pro-angiogenic dcTRAIL-R1+ neutrophils while activating antigen-presenting CD74+ neutrophil populations. The engineered system elicites coordinated immunomodulation through multiple mechanisms: (1) promoting dendritic cell maturation, (2) increasing CD74+ neutrophil populations, (3) inducing macrophage polarization from M2 to M1 phenotypes, and (4) enhancing tumor infiltration of CD8+ T cells and natural killer cells. This study reveals that bacteria-tumor metabolic crosstalk upregulates beneficial metabolites, notably leucine, which promotes phenotypic reprogramming of neutrophils toward the antigen‑presenting CD74+ subset, thereby bridging innate metabolic regulation with adaptive antitumor immunity. This finding goes beyond the material-centric logic of previous probiotic-nanomaterial systems and establishes a metabolism-centric framework for bacteria‑mediated cancer immunotherapy.

Streptococcus suis, a significant zoonotic pathogen, annually caused substantial economic losses in the swine industry and had intensified threat to public health due to the recent emergence of human-associated clade. In this study, we discovered that the rare-earth metal-based metal-organic frameworks (Y-BTC) possessed excellent ECL capabilities. After prereduction at high voltage, its ECL intensity was enhanced by two times. Subsequently, we developed an efficient CRISPR/Cas12a-mediated electrochemiluminescence resonance energy transfer (ECL-RET) biosensor utilizing Y-BTC for the detection of the human-associated S. suis clade. Y-BTC was employed as the ECL-RET donor and ECL emitter, and the spherical nucleic acid Au NP was utilized as the ECL-RET receptor. In the presence of the target, isothermal amplification was triggered to generate a large number of amplicons, which subsequently activated the trans-cleavage activity of Cas12a. Cas12a cleaved the nucleic acid shell on the surface of Au NPs, reducing the spatial distance between Au NPs and Y-BTC due to electrostatic adsorption, thereby quenching the ECL of Y-BTC via ECL-RET. Consequently, the presence of targets can be observed by a reduced ECL signal. The sensor exhibited a detection range of 25 pM to 50 nM, with a detection limit as low as 17 pM. The practical utility was verified through actual sample testing. Our proposed ECL-RET sensing strategy provides a new avenue for the sensitive detection of S. suis. The universality has also been demonstrated using Fusobacterium nucleatum, Salmonella pullorum, and Listeria monocytogenes, holding great promise in the field of food safety and public health.

The rapid spread of drug-resistant bacterial infections has become a major global health challenge, particularly in the treatment of deep organ abscesses, which often lead to severe and life-threatening infections. Traditional light-responsive and microenvironment-responsive nanoparticle drug delivery systems (DDSs) have limitations in treating deep abscesses. In contrast, ultrasound (US)-driven sonodynamic therapy (SDT), with its non-invasive, targeted radiation and excellent tissue penetration capabilities, offers great potential for eradicating deep bacterial infections. This study proposes an ultrasound-driven manganese-based nanoparticle drug delivery system (AMP) for the effective treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. The core of the system is manganese oxide (MnOx) nanoflowers, which serve as the nanoparticle carrier, loaded with the antimicrobial non-antibiotic drug auranofin, and surface-modified with polyethylene glycol to enhance its biocompatibility and drug delivery performance. AMP demonstrates significant antibacterial activity in vitro and effectively promotes wound healing under US-driven stimulation. Furthermore, the potential antibacterial and wound-healing mechanisms of AMP are revealed for the first time. This study cleverly combines non-antibiotic drugs with inorganic nanomaterials to successfully achieve efficient SDT, providing a new and effective strategy for treating deep bacterial infections.

Rabies, a zoonotic infectious disease of the central nervous system caused by the rabies virus (RABV), remains an acute infectious disease with the highest human mortality rate to date. Nonetheless, the detection of RABV has continued to present significant challenges. Herein, we developed a dual-mode electrochemiluminescence (ECL) and fluorescence (FL) biosensor utilizing dendritic mesoporous UiO-66 (DMAUiO) as an ECL nanoreactor. This system integrated a CRISPR/Cas12a-driven mimic-hybridization chain reaction (mimic-HCR) isothermal amplification strategy for the highly sensitive detection of the RABV nucleoprotein (RABV-N) gene. The prepared DMAUiO nanoreactor exhibited a rich pore structure that facilitated efficient loading of luminol (Lu) and enabled rapid diffusion of coreactants into its channels. In the presence of RABV-N, mimic-HCR-mediated isothermal amplification generated abundant output DNA, which activated the trans-cleavage activity of the Cas12a protein. Subsequently, activated Cas12a cleaved the magnetic DNA assembly (MDA), releasing 6-carboxyfluorescein (FAM) and dopamine (DA), where DA specifically functioned as an ECL quencher. This cleavage event led to FL signal recovery and ECL signal quenching, enabling dual-mode detection. The developed biosensor achieved linear detection ranges of 0.5 pM-8 nM (ECL) and 5 pM-10 nM (FL) for RABV-N, with detection limits of 0.17 and 4.1 pM, respectively. Our proposed dual-mode biosensor demonstrated excellent practicability in rat cerebrospinal fluid samples, providing a novel analytical platform for rabies diagnosis and biological analysis.

Rabies, caused by rabies virus (RABV), is a zoonotic disease with a high mortality rate that has attracted global attention with the goal of eradication by 2030. However, rabies can only be prevented by appropriate and multiple vaccinations, which impede widespread vaccination in developing countries due to its high expenditure. Designing single-dose vaccines is a pressing challenge in the prevention of rabies and other infectious diseases. Herein, a metal-phenolic network (MPN)-based hydrogel vaccine (designated as CGMR) was developed to stimulate potent humoral immunity against RABV infection by a single immunization, resulting in 4.3-fold and 1.8-fold enhancements of virus-neutralizing antibody compared with that induced by inactivated RABV and alum adjuvant. The CGMR, cross-linked by phenol-modified chitosan with manganese ion, could prolong residence time by confining the antigen to the network of hydrogel, acting as a "hydrogel antigen depot". It also stimulated the activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway, facilitating dendritic cell maturation and antigen presentation. The vaccine formulation recruited immunocytes and activated the germinal center, enhancing and sustaining humoral immune responses against the virulent RABV challenge. Collectively, this injectable manganese-based hydrogel vaccine provides a universal and ideal avenue for rabies and other infectious diseases.

Designing advanced biomimetic nanoplatforms that combine photothermal therapy (PTT) and immune activation represents a modern approach to addressing the challenges of cancer therapy. This study presents a nanobiomimetic hollow copper-sulfide (HCuS) platform for precise homotypic tumor targeting and melanoma treatment. The HCuS@OVA@CM (COC) nanoplatform-encapsulated ovalbumin (OVA) antigen protein within HCuS nanoparticles and was coated with melanoma cell membranes (B16F10). Importantly, this design facilitates specific tumor accumulation and achieves 16.0% photothermal conversion efficiency under 1064 nm NIR-II irradiation, which is a key factor for therapeutic success. In vitro studies have demonstrated that this nanoplatform induces immunogenic cell death (ICD), enhances antigen presentation, and stimulates dendritic cell (DCs) maturation. In vivo experiments confirmed that COC-mediated NIR-II photothermal treatment significantly suppressed tumor growth without notable body weight loss. This biomimetic nanoplatform approach offers a targeted, enhanced, and effective immune response for tumor photothermal immunotherapy, making it a promising candidate for advanced melanoma treatment and anticancer therapy.

Huanglongbing (HLB) poses a catastrophic threat to the global citrus industry, necessitating early detection of pathogen for disease control and minimize economic losses. Herein, we reported a one-pot electrochemiluminescence (ECL) biosensor for integrating rolling circle amplification (RCA)-activated CRISPR/Cas12a dual cleavage activity, and engineered magnetic beads-based quenched ECL emitter. Target-initiated RCA generated amplicons that activated Cas12a, simultaneously leveraging cis-cleavage for template recycling and trans-cleavage to degrade single stranded DNA attached on Ru(bpy)32+-loaded magnetic beads. This dual-amplification strategy restored ECL signals, enabling ultrasensitive detection of Candidatus Liberibacter asiaticus (CLas) ribonucleotide-diphosphate reductase subunit beta gene fragments with high specificity. A linear range 10 fM-1 nM with the detection limit of 2 fM was obtained. The integrated platform eliminated multi-step incubations, and exhibited satisfactory performance in citrus leaf samples, offering a powerful tool for HLB diagnostics.

Drug-resistant bacterial pneumonia presents a substantial challenge for targeted drug delivery to the infected lung site due to the existence of mucus and gas-blood barriers. Allicin, renowned for its extensive bioactivity, holds promise as an antimicrobial agent. However, its unregulated bioavailability restricts both its antibacterial and anti-inflammatory efficacy. As a result, precise targeting of the infection site for controlled drug release is crucial in the treatment of drug-resistant bacterial pneumonia. In this study, we developed a macrophage cell membrane-modified nanoallicin composite material (Allicin@MSN@CM) by utilizing cell membrane modification technology. By harnessing the homing ability of macrophage cell membranes to inflammatory sites, we enabled the active aggregation of nanomaterials during circulation within the body. Furthermore, alpha-hemolysin secreted by MRSA bacteria was employed to perforate the cell membrane, facilitating on-demand drug release at the infection site. In vitro antibacterial experiments demonstrated that the material possesses strong antibacterial properties, alongside good stability and biocompatibility. Additionally, in a mouse model of lung infection, it not only effectively eradicated bacteria but also reduced lung inflammation. This study provides valuable insights into the application of nanocarriers in delivering traditional Chinese medicine to address the challenges posed by bacterial drug-resistant pneumonia.

Drug-resistant bacterial infections pose a significant threat to global health, creating an urgent need for new antimicrobial agents. Reusing approved drugs has gained attention as a strategy to address this issue. In this study, a nano antibacterial platform (DSF@HKUST-1@Dex) that responds to the infection microenvironment is proposed. This platform releases disulfiram (DSF), binds to copper ions in the mildly acidic conditions of infected areas, converting DSF from nontoxic to toxic in situ, thereby inducing bacterial death and enhancing copper ion absorption. Noncatalytic treatment is also initiated for a synergistic antibacterial effect. Excessive copper ions disrupt bacterial metabolism, inhibit the Tricarboxylic acid (TCA) cycle, reduce ATP levels, and induce cuproptosis-like death, significantly enhancing antibacterial efficacy. In a bacterial wound infection model, the platform exhibited excellent antibacterial activity, promoting wound healing and reducing inflammation. Proteomic analysis showed that the platform selectively targeted bacterial peptidoglycan, disrupted the bacterial cell wall, impacted energy metabolism, and inhibited bacterial growth. In conclusion, this nanoplatform offers a promising strategy for treating drug-resistant infections by repurposing old drugs, converting them to toxic forms, and providing a novel antimicrobial approach.

Due to its complex pathogenesis involving dysregulated reactive oxygen species(ROS)storms,cytokine hyperactivation and immune cell infiltration,acute lung injury(ALI)presents critical clinical challenges,and conventional therapies often fail to address the dual requirements of precise inflammatory targeting and microenvironment regulation.Herein,we report an intelligent biomimetic nanosystem(CeGM)featuring(i)synergistic catalytic circuits,where hollow CeO2 nanoenzymes are combined with glycyrrhizic acid(GA)through density functional theory(DFT)-optimized binding configurations,achieving charge redistribution-induced dual-site catalytic activation relative to conventional CeO2 alone;(ii)pathology-responsive delivery,where macrophage membrane camouflage enables lipopolysaccharide(LPS)recognition and inflammatory chemotaxis,yielding 7.8-fold higher alveolar accumulation than non-coated counterparts in LPS-induced ALI models;(iii)multidimensional immunomodulation,where NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome activation(56.20%interleukin-1β(IL-1β)reduction)and M1 macrophage polarization(2.4-fold M2/M1 ratio increase)are concurrently suppressed through GA-mediated nuclear factor kappa B(NF-κB)pathway inhibition and CeO2-mediated redox homeostasis restoration.This dual-functional nanoplatform demonstrates favourable therapeutic outcomes in mitigating pulmonary edema by clearing ROS(47.20%reduction in ROS levels),neutrophil infiltration(58.16%myeloperoxidase(MPO)activity decrease)and cytokine storms(tumor necrosis factor-alpha(TNF-α)reduction of 45.90%),offering a paradigm-shifting strategy for precision nanomedicine in acute inflammatory disorders.

The development of advanced wound dressings that incorporate synergistic antibacterial strategies is essential for addressing antibiotic-resistant infections and facilitating tissue regeneration. This study presents a near-infrared (NIR)-responsive double-network hydrogel (Gel@HS) that combines photothermal therapy (PTT) and nitric oxide (NO) gas therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The hydrogel was engineered with acrylamide as the primary network and chitosan, a carbohydrate polymer, as the secondary network, capitalizing on chitosan's natural tissue adhesion and antibacterial properties. Hollow copper sulfide nanoparticles (HCuS) and sodium nitroprusside (SNP) were incorporated to enable photothermal conversion and controlled NO release upon NIR irradiation. The hydrogel demonstrated remarkable mechanical stability, adhesion, and targeted antibacterial activity, facilitating bacterial eradication through PTT-induced membrane disruption and NO-mediated protein inactivation. In vitro experiments confirmed its broad-spectrum antibacterial efficacy (>99 % MRSA elimination) and anti-inflammatory effects via macrophage modulation. In vivo testing using an MRSA-infected murine wound model showed accelerated healing (93 % wound closure within 9 days), reduced bacterial load, and diminished inflammatory cytokine levels. This research highlights the potential of carbohydrate polymer-based hydrogels as multifunctional platforms for combating resistant infections and promoting wound healing through physicochemical synergy.

Objective Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen in local and pulmonary infections following craniofacial surgery, and antibiotic resistance can significantly hinder patient recovery. Berberine, a broad-spectrum antibacterial agent from traditional Chinese medicine, has been clinically used for decades but suffers from low bioavailability. Metal-organic frameworks (MOFs), with their high surface area and porosity, enable high drug loading and targeted release under specific conditions but are rapidly cleared from circulation. By coating MOFs with macrophage membranes, immune-evasion signals are mimicked, reducing clearance rates. This cell membrane-coated MOF drug delivery system allows berberine to specifically target infected areas, evade phagocytosis, and effectively combat infections. Methods Using a one-pot synthesis method, zeolitic imidazolate framework-8 (ZIF-8) co-loaded with berberine and glycyrrhizinate (Ber&Gly@ZIF-8) was synthesized and coated with RAW 264.7 macrophage membranes to form Ber&Gly@ZIF-8@CM (BGZC). The nanomaterials were characterized using dynamic light scattering, ultraviolet spectrophotometry, Fourier-transform infrared spectroscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, and transmission electron microscopy. Antibacterial activity against MRSA was tested via colony forming unit (CFU), live/dead staining, and electron microscopy. Cytocompatibility was assessed via hemolysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. A murine lung infection model evaluated targeting and therapeutic efficacy. Results The average particle size of BGZC was approximately 200 nm. At a concentration of 100 µg/mL, the material exhibited a 99.5% bactericidal efficacy. The hemolysis rate was less than 5%, and at a concentration of 50 µg/mL, the survival rate of human normal lung epithelial cells (BEAS-2B) exceeded 90%. Additionally, the internalization rate of the material by RAW 264.7 cells was 10.88%, which was lower than the 22.56% observed in the group without cell membrane coating. In infected mice, BGZC accumulated in inflamed lungs, reducing bacterial load and consolidation without systemic toxicity (normal blood parameters and organ histology). Uninfected mice showed liver-focused accumulation. Conclusions BGZC exhibits excellent targeting ability for infections and good biocompatibility, effectively reducing bacterial load and alleviating lung inflammation. It shows potential for treating local and pulmonary infections following craniofacial surgery. Clinical significance This macrophage-coated MOF nanoplatform enables targeted, biocompatible delivery of berberine, offering a promising strategy for treating drug-resistant infections after craniofacial surgery with reduced systemic toxicity.

Nanoparticles of biological origin exhibit many unique properties in biological applications due to their exquisite structure, specific composition, and natural biological functionality. In this study, we obtained lysosomes from three distinct cell types (one normal cell and two activated immune cells) and demonstrated their potential as natural therapeutic nanoparticles for tumor therapy. In vitro experiments revealed that these lysosomes maintained their structural integrity, were well-distributed, and exhibited significant biological activity, which effectively induced cancer cell death by generating ROS and disrupting biological substrates. Additionally, in vivo investigations showed that these lysosomes could accumulate in tumor tissues after intravenous administration and exhibited exceptional therapeutic effects through the destruction of tumor blood vessels and the degradation of immunosuppressive proteins, with complete tumor disappearance in a single treatment. This research on the utilization of bioactive lysosomes for tumor treatment provides valuable insights into drug development and tumor treatment, particularly when conventional approaches have proven ineffective.

Huanglongbing (HLB) is a severe disease in Citrus caused by the infection of Candidatus Liberibacter asiaticus (CLas), which has brought about substantial economic losses in the global Citrus industry. Recently, HLB has been recognized as a plant immune-mediated disease resulting from the CLas-colonization stimulated immune responses and the accumulation of excessive reactive oxygen species (ROS) in Citrus tissues. Here, we report a manganese oxide nanozyme (MONPs) based strategy to scavenge and regulate the ROS metabolism in HLB infected Citrus, thereby protecting leaf tissues against oxidative stress. Transmission electron microscopy (TEM) imaging revealed that MONPs enable efficient delivery into the intercellular space by spraying dispersion. ROS detection indicated the direct ROS scavenging ability of MONPs with high efficiency in HLB-Citrus with about 60% of ROS decreasing. Enzyme activation and gene expression analysis exhibited that the MONP treatment could regulate the ROS metabolism gene in Citrus to alleviate oxidative stress. Current research demonstrated that the HLB-Citrus sprayed with MONPs showed a noticeable protective effect within 22 days to alleviate the blotchy mottle symptoms. Furthermore, various physiological indexes such as MDA, starch, total soluble sugar, carotenoid and chlorophyll in HLB-Citrus leaves exhibited significant improvement post-MONP treatment. This MONP-based approach provides a promising alternative strategy to modulate and mitigate oxidative stress in HLB-Citrus, thereby serving the Citrus industry.

During the previous two decades, nanotechnology has significantly improved. Several studies have also conducted extensive investigations into the clinical uses of these nanotechnologies for cancer detection, diagnosis, and therapy. These materials, known as porous coordination polymers (PCPs), possess various advantageous properties, such as regular topology and controllable channel diameters and shapes, designable surface functionality, and adaptable frameworks. These characteristics make them ideal for precision polymer production and specific polymer confinement applications. These materials' prospective applications have been investigated in various fields, for instance, drug administration and sensing, luminescence, catalysis, and ionic and electrochemical conductivity. Their ability to be customized in terms of size, controllable drug release rates, improved therapeutic efficacy, elevated agent loadings, surface chemistry, and augmented tumor accumulation via inert tumor targeting, enhanced penetrability, and retention (EPR) effect make them a promising material for biomedical use. We will discuss the remarkable properties of PCPs as a therapeutic agents, surface modification of PCPs as nanocarriers, PCPs for cancer rehabilitation, and PCPs as drug delivery systems (chemotherapy, photodynamic therapy (PDT), nucleic acid delivery, nitric oxide (NO) delivery, and drug delivery of other drugs) in this book chapter.

Citrus Huanglongbing (HLB) is known as the cancer of citrus, where Candidatus Liberibacter asiaticus (CLas) is the most prevalent strain causing HLB. In this study, we report a novel electrochemiluminescence (ECL) biosensor for the highly sensitive detection of the CLas outer membrane protein (Omp) gene by coupling rolling circle amplification (RCA) with a CRISPR/Cas12a-responsive smart DNA hydrogel. In the presence of the target, a large number of amplicons are generated through RCA. The amplicons activate the trans-cleavage activity of CRISPR/Cas12a through hybridizing with crRNA, triggering the response of smart DNA hydrogel to release the encapsulated AuAg nanoclusters (AuAg NCs) on the electrode and therefore leading to a decreased ECL signal. The ECL intensity change (I0 - I) is positively correlated with the concentration of the target in the range 50 fM to 5 nM, with a limit of detection of 40 fM. The performance of the sensor has also been evaluated with 10 samples of live citrus leaves (five HLB negative and five HLB positive), and the result is in excellent agreement with the gold standard qPCR result. The sensing strategy has expanded the ECL versatility for detecting varying levels of dsDNA or ssDNA in plants with high sensitivity.

The complications of pulmonary thrombosis caused by the coronavirus pneumonia have created an unprecedented clinical need for efficient targeted therapy of pulmonary thrombosis. Here, we designed an inhalable engineered platelet nanomotor (MHLP) that could mimic platelet function to cross the pulmonary mucosal barrier and target pulmonary thrombus. The MHLP could respond to the thrombotic microenvironment by using reactive oxygen species as the fuel to produce oxygen and nitric oxide for promoting the release of the loaded anticoagulant drug hirudin. These gases can also regulate the thrombo-inflammatory microenvironment, promote the polarization of macrophages from pro-inflammatory to anti-inflammatory phenotype, and downregulate the expression level of inflammatory factors. Through the two-pronged strategy of anticoagulation and regulation of the inflammatory microenvironment, MHLP demonstrates the effect of safely dissolving pulmonary thrombus and preventing recurrence.

Food safety has recently become a widespread concern among consumers. Surface-enhanced Raman scattering (SERS) is a rapidly developing novel spectroscopic analysis technique with high sensitivity, an ability to provide molecular fingerprint spectra, and resistance to photobleaching, offering broad application prospects in rapid trace detection. With the interdisciplinary development of nanomaterials and biotechnology, the detection performance of SERS biosensors has improved significantly. This review describes the advantages of nanomaterial-based SERS detection technology and SERS’s latest applications in the detection of biological and chemical contaminants, the identification of foodborne pathogens, the authentication and quality control of food, and the safety assessment of food packaging materials. Finally, the challenges and prospects of constructing and applying nanomaterial-based SERS sensing platforms in the field of food safety detection are discussed with the aim of early detection and ultimate control of foodborne diseases.

INTRODUCTION:Diaphorina citri is the most serious pest of citrus worldwide because it is the natural insect vector of huanglongbing. Cycloxaprid (Cyc) was highly toxic to D. citri. However, the poor solubility and stability had limited its development. OBJECTIVES:In order to improve the insecticidal effect and stability to harsh climatic conditions of Cyc. METHODS:Cyc was chosen as the representative pesticide, 4,4'-methylenebis (phenyl isocyanate), PEG-600 and n-butanol were used to prepare sustained-release nano-gelation particles (Cyc@NGs). RESULTS:Cyc@NGs enhance the toxicity of Cyc more than 3 folds. Furthermore, Cyc@NGs showed excellent anti-rain and anti-UV capacity. After being exposed to ultraviolet light for 12 h, Cyc decreased by 100 %, while the insecticide content of Cyc@NGs only decreased by 25 %. Additionally, Cyc@NGs possessed better wettability on citrus leaves, mainly benefitting from its lower contact angle on citrus leaves. Moreover, FITC-labeled nano-gelation particles (FITC-NGs) exhibited high capability to penetrate and enrich in citrus leaf tissue and D. citri midgut. Consequently, NGs promoted the translocation and durability of insecticides, thereby, increasing the insecticidal activity. The results suggested that nano-gelation particle is a promising platform to deliver insecticides and Cyc@NGs would be the suitable candidate for the effective management of D. citri.

AbstractFrequent intravesical chemotherapy is still the adopted clinical option after bladder cancer surgery with low adhesion, poor selectivity, low permeability, and drug resistance. Herein, we develop an ingenious bladder cancer dissociation method to enhance intravesical chemotherapy and tumor self‐exclusion with urine. Ethylene diamine tetraacetic acid (EDTA), a common Ca2+ chelator, is loaded with the typical clinical bladder instillation drug doxorubicin (Dox) in chitosan‐modified hollow gold nanorods and subsequently coated with cancer cell membranes. After bladder perfusion, the nanoplatform exhibits high affinity toward bladder tumors under homologous targeting, assisting in long‐term retention. Under NIR‐II laser irradiation, the photothermal effect accelerates the unloading of cargo, and the released EDTA then disrupts intratumoral junctions by depriving and chelating Ca2+ from the intercellular calcium‐dependent connexin. The consequential intertumoral dissociation gives access to the deeper penetration of Dox and allows the exclusion of the shed small tumor masses from the body with the urine. This distinctive tumor dissociation concept holds great promise for modern clinical intravesical chemotherapy and perhaps for other gastrointestinal malignancies.