Urological cancers, together with bladder, prostate, and kidney cancers, symbolize a significant international well being burden. In keeping with the newest GLOBOCAN 2024 report, bladder most cancers accounts for roughly 615,000 new circumstances and 230,000 deaths annually, rating tenth amongst all malignancies. Prostate most cancers stays essentially the most ceaselessly recognized urological most cancers in males, with round 1.47 million new circumstances yearly, whereas kidney most cancers contributes to over 430,000 new circumstances worldwide. Regardless of advances in prognosis and therapy, excessive recurrence charges and therapeutic resistance stay key medical challenges, underscoring the pressing want for revolutionary therapeutic methods [1], [2], [3].
Bladder most cancers is the tenth commonest malignancy, predominantly affecting males, and roughly 75 % of latest circumstances are recognized as non–muscle-invasive bladder most cancers (NMIBC) [4], usually managed with transurethral resection of bladder tumor (TURBT) mixed with intravesical chemotherapy or immunotherapy [5], [6]. Nevertheless, recurrence stays a significant problem, with 5-year charges as excessive as 50–70 % [7]. In RCC, localized illness can typically be successfully handled with radical or nephron-sparing partial nephrectomy, yielding favorable long-term outcomes [8]. Nonetheless, dangers of residual lesions or recurrence persist, significantly in multifocal tumors with tubular infiltration or vascular invasion, or when advanced anatomy limits full resection [9], [10]. Superior or metastatic RCC is primarily managed with systemic therapies resembling tyrosine kinase inhibitors and immune checkpoint inhibitors [11], [12], but therapeutic resistance and the immunologically “chilly” tumor microenvironment considerably limit therapy efficacy, necessitating combinatorial and microenvironment-modulating methods to enhance responses [13], [14]. PCa is characterised by indolent development, medical heterogeneity, and sometimes asymptomatic early phases [15], [16]. Whereas localized illness could also be cured with prostatectomy or radiotherapy, 20 %–40 % of sufferers expertise biochemical recurrence (BCR) inside 5 years, as indicated by prostate-specific antigen (PSA) monitoring [17]. Development to castration-resistant prostate most cancers (CRPC) is a deadly stage characterised by lack of androgen dependence, elevated aggressiveness, and resistance to traditional therapies [18]. Regardless of interventions focusing on the androgen receptor axis, chemotherapy, and bone metastases, sturdy illness management stays elusive [19]. Collectively, these challenges underscore the pressing want for revolutionary therapeutic platforms able to modulating the tumor microenvironment, activating antitumor immunity, and reaching localized management to enhance medical outcomes in urological malignancies.
Current research have revealed that urological tumors share distinct TME traits, together with hypoxia, acidic pH, excessive hydrogen peroxide (H2O2) ranges, and glutathione (GSH) enrichment [20], [21]. These lesion-specific alterations supply promising alternatives for the event of tumor-responsive therapeutic methods. Amongst them, nanocatalytic platforms, represented by nanozymes, have attracted growing consideration due to their enzyme-mimicking actions, together with peroxidase-, oxidase-, and glutathione oxidase-like catalytic reactions. These platforms can effectively set off cascade catalytic reactions that convert endogenous substrates into reactive oxygen species (ROS) throughout the TME, thereby inducing ferroptosis and cuproptosis. Along with their therapeutic exercise, additionally they possess multifunctional capabilities, together with cascade-driven sign amplification, focused supply, and microenvironmental responsiveness, making them core enablers of built-in theranostic approaches [22], [23]. Owing to their wonderful structural tunability and organic adaptability, nanocatalytic platforms supply distinct benefits for the exact prognosis and therapy of urological cancers [24]. They are often domestically administered by way of intravesical instillation or transurethral perfusion, making them significantly appropriate for treating cavity-type or domestically superior tumors resembling bladder and prostate cancers. This localized supply tremendously enhances the drug focus on the tumor web site, prolongs the retention time, and minimizes systemic toxicity, thereby bettering affected person tolerance and compliance. Systemic supply by way of intravenous injection can also be possible, permitting passive tumor focusing on by the improved permeability and retention (EPR) impact [25]. Furthermore, floor modification with tumor-homing peptides can endow the platform with energetic focusing on capabilities, enhancing tumor accumulation and precision of intracellular supply [26], [27]. These methods are particularly efficient within the extremely vascularized or ECM-rich environments typical of urological tumors. Importantly, sure nanocatalytic supplies—resembling Fe3O4, MnO2 and CeO2 nanozyme programs—intrinsically possess multimodal imaging capabilities, together with T1/T2-weighted magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and computed tomography (CT) [28], [29], [30], [31], [32], [33], [34], [35], [36], [37]. These imaging functionalities allow real-time visualization of drug launch and catalytic processes, thereby facilitating exact and image-guided remedy.
Owing to the superb peroxidase (POD)-like and oxidase (OXD)-like catalytic actions of sure nanozymes, they’ve demonstrated nice potential within the noninvasive prognosis of ailments [38], [39]. Specifically, they permit the speedy detection of tumor-associated metabolites and molecular biomarkers in urine samples. Lately, researchers have developed a wide range of nanozyme-based diagnostic platforms, starting from visible to instrument-assisted methods, together with colorimetric immunoassays (CIAs), lateral circulation immunoassays (LFIAs), paper-based analytical units (dPADs), sandwich-type electrochemical immunosensors, surface-enhanced Raman scattering (SERS), and laser desorption/ionization mass spectrometry (LDI-MS). In these programs, nanozymes usually catalyze the manufacturing of sign amplifiers resembling H2O2 or hydroxyl radicals (·OH) in urine, enabling extremely delicate detection. For instance, sarcosine, a key urinary biomarker of prostate most cancers, could be detected by way of nanozymes with sarcosine oxidase-like (SOX-like) exercise, which catalyze the oxidation of sarcosine to generate H2O2. The ensuing H2O2 can then set off chromogenic reactions by way of POD/Fenton-type mechanisms or induce electrochemical responses, forming the premise of cascade diagnostic platforms for prostate most cancers screening [40], [41], [42], [43], [44], [45], [46]. To deal with the medical calls for for quantitative accuracy and anti-interference efficiency, researchers have built-in nanozyme catalysis with high-performance sign transduction methods, resulting in the event of multimodal diagnostic programs resembling electrochemical detection (ECL) and ratiometric fluorescence (RF) sensing [47]. Electrochemical platforms typically depend on nanozymes immobilized on electrode surfaces to amplify the detection of urinary analytes, together with sarcosine, PSA, miRNAs, and different related biomarkers, providing the benefits of excessive sensitivity, speedy response, and transportable operation. RF programs, alternatively, make the most of dual-fluorescence channels, the place nanozyme-mediated fluorescence enhancement or quenching is internally referenced to realize self-calibration and exact quantification. These versatile platforms, when mixed with urine samples, supply noninvasive, high-throughput, and clinically translatable diagnostic options, offering robust technical assist for early most cancers screening, biochemical relapse monitoring, and customized intervention in urological oncology [48], [49], [50].
Constructing on this basis, this assessment systematically summarizes current advances in nanozyme-based methods for the prognosis and remedy of urological tumors, specializing in the next key areas: (1) basic catalytic mechanisms and materials classifications of nanozymes; (2) catalytic therapies and their synergistic mechanisms with photothermal, photodynamic, or immunotherapies, in addition to associated case research; (3) methods for imaging enhancement and biomarker detection, together with consultant examples; and (4) present challenges and potential instructions for future improvement. Not like earlier critiques that primarily summarize basic nanozyme rules or their purposes in oncology, this work particularly focuses on tumor microenvironment–responsive nanozyme programs for urological cancers. It highlights how catalytic mechanisms and materials designs have advanced to assist cascade therapeutic methods, imaging-guided interventions, and urine-based diagnostic purposes. By integrating discussions on ferroptosis, immune modulation, and multimodal catalysis, this assessment gives a complete and comparative perspective that bridges basic catalytic science with clinically oriented nanomedicine. The purpose is to stipulate present progress, establish persistent challenges, and suggest future instructions towards clever, urine-compatible, and translational nanozyme platforms for precision urologic oncology.
