Pheochromocytoma is a rare adrenal medullary neoplasm in cats, with limited published cases and diagnostic challenges due to variable clinical presentation. An 8-year-old neutered male domestic shorthair cat presented with severe watery diarrhea, lethargy, and anorexia. Diagnostic evaluation revealed chronic kidney disease, pyelonephritis, and a large cystic right adrenal mass identified on ultrasonography and computed tomography. Endocrine testing did not support hyperadrenocorticism or hyperaldosteronism, and functional assessment of catecholamine excess was not performed. Surgical adrenalectomy was elected due to mass size and rupture risk. Histopathological examination demonstrated a medullary adrenal neoplasm composed of polygonal cells arranged in characteristic packets. Immunohistochemistry revealed synaptophysin positivity with negative chromogranin A staining, supporting a diagnosis of pheochromocytoma. Postoperative recovery was uneventful, and the cat remained normotensive and clinically stable at one year, with chronic kidney disease managed medically. This case underscores the diagnostic complexity of feline pheochromocytoma and highlights the importance of integrating imaging, histopathology, and immunohistochemistry, as chromogranin A negativity does not exclude this diagnosis.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by poor prognosis and limited responsiveness to conventional therapies. Increasing evidence shows that the reprogramming of glucose metabolism is a hallmark of cancer cells, supporting their rapid proliferation, metastatic potential, and therapy resistance. This metabolic shift is particularly pronounced in TNBC, where reliance on glycolysis is greater than in other breast cancer subtypes. Consequently, strategies that target glucose metabolic pathways may offer a promising means to overcome treatment resistance and improve clinical outcomes. In this review, we summarize the unique features and regulatory mechanisms of glycolytic reprogramming in TNBC, with attention to tumor heterogeneity and its implications for disease progression and treatment response. We highlight recent preclinical studies that evaluate therapeutic approaches designed to exploit metabolic vulnerabilities, including glycolysis inhibition, metabolic enzyme targeting, and combination regimens with radiotherapy. Collectively, these findings suggest that interventions aimed at glycolytic pathways hold considerable potential to enhance radiosensitivity in TNBC. We discuss the translational prospects of this research, emphasizing the value of glycolysis-related genes as predictive biomarkers and as foundations for the development of novel targeted agents. While preliminary evidence is encouraging, further validation is required to establish the safety, efficacy, and clinical applicability of these strategies in human patients. Continued research in this area is expected to contribute to the development of more effective therapeutic options, ultimately improving the management and prognosis of TNBC.

Heparin, a polydisperse glycosaminoglycan, is well-known for its anticoagulant activity and clinical use in preventing venous thromboembolism. In addition to coagulation, heparin and its derivatives have shown therapeutic potential in cancer and infectious, inflammatory, and neurodegenerative diseases. This study aimed to develop and evaluate heparin-capped AgNPs (hep-AgNPs) as multifunctional nanotherapeutics with selective cytotoxicity, antibacterial, and antifungal activity.

Heparin was covalently conjugated to cysteamine-terminated silver nanoparticles via MES-buffer-mediated amide coupling, providing a mild, aqueous alternative to conventional DMF-based methods. The nanoparticles were characterised by UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), dynamic light scattering (DLS), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) analyses. The colloidal stability was assessed over a broad range of pH values. The biological performance of hep-AgNPs was evaluated in vitro against a triple-negative breast cancer (TNBC) cell line (MDA-MB-231), a double-positive cell line (MCF-7), and normal breast cells (MCF-10A), and microbial strains, including Salmonella typhimurium, E. coli, Aspergillus fumigatus, and Candida albicans.

The synthesised hep-AgNPs exhibited high yield, effective heparin surface functionalization, and excellent colloidal stability at physiological pH, with stability systematically assessed across a broad pH range. Hep-AgNPs demonstrated time and concentration-dependent selective cytotoxicity, toward breast cancer cells, including MCF-7 and triple-negative MDA-MB-231, with a favourable selectivity index (>1) compared to MCF-10A cells, and the strongest selectivity observed in the TNBC model at 48 h. In addition, hep-AgNPs showed potent antibacterial activity (IC₅₀ = 24.3 µg/mL) and antifungal activity (IC₅₀ = 6.2 µg/mL for A. fumigatus and 24.43 µg/mL for C. albicans). In addition, they exhibit strong biocompatibility with keratinocytes and fibroblasts.

Heparin-capped silver nanoparticles combine the biological functionality of heparin with the antimicrobial and selective cytotoxic properties of the silver nanoparticles. Their selective cytotoxicity, antimicrobial efficacy, and favourable cellular interaction profiles highlight their potential as multifunctional nanoplatforms for applications such as chronic wound management in neutral to alkaline wound environments, and dose-controlled, targeted therapeutic strategies relevant to aggressive cancer models, including TNBC.

Mitochondria serve as cellular powerhouses and function as central hubs for oxidative metabolism and signaling regulation. These organelles produce ATP primarily through oxidative phosphorylation (OXPHOS), thereby fueling cellular growth and function. In cancer, metabolic reprogramming drives malignant progression, with mitochondria playing a pivotal role. To meet heightened energy and biosynthetic demands, cancer cells modulate mitochondrial OXPHOS activity while enhancing fatty acid oxidation and amino acid metabolism, thereby maintaining redox balance and supporting survival and proliferation. Targeting mitochondrial metabolism with nanomaterials has emerged as a promising strategy for cancer therapy. This review covers advances from 2018-2025, encompassing lipid-based, polymeric, peptide-functionalized, and stimuli-responsive nanocarriers. By employing nanocarriers to deliver metabolic inhibitors or chemotherapeutic agents precisely to mitochondria, this approach can disrupt energy metabolism, impair redox homeostasis, or induce apoptosis in tumor cells. Such targeted intervention not only enhances chemotherapy efficacy but also synergizes with radiotherapy and immunotherapy, offering a potential route to overcome resistance. Despite its considerable promise, several challenges remain in the nanomaterial-based targeting of mitochondrial metabolism, including optimization of targeting efficiency and biosafety. Future efforts should focus on refining these aspects to accelerate the clinical translation of precise mitochondrial metabolism-directed therapies.

Doxorubicin (DOX) is a cornerstone chemotherapeutic for breast cancer; however, its clinical efficacy is limited by inefficient intracellular delivery and dose-limiting off-target toxicity. Microenvironment-responsive nanoplatforms offer a promising strategy to enhance tumor selectivity and therapeutic performance.

A core-shell nanosystem (UTMD) was constructed by coating an NH₂-MIL-88B(Fe) metal-organic framework (Fe-MOF) shell onto a UCNP@TiO₂ scaffold. The Fe-MOF shell was designed as a dual pH- and glutathione (GSH)-responsive gatekeeper for controlled DOX release. The nanosystem was characterized for structural features, drug loading, and stimulus-responsive release behavior. Cellular uptake, intracellular trafficking, cytotoxicity, and redox-related biochemical changes were evaluated in MCF-7 breast cancer cells and HEK-293 normal cells.

UTMD achieved high encapsulation efficiency (86.5%) and maintained stability under physiological conditions, while enabling accelerated DOX release in acidic and reducing environments. The nanosystem enhanced cellular internalization and promoted nuclear accumulation of DOX in MCF-7 cells. In addition, UTMD induced significant intracellular redox imbalance, characterized by GSH depletion, increased reactive oxygen species levels, and elevated lipid peroxidation, accompanied by mitochondrial membrane potential depolarization. These changes are consistent with ferroptosis-associated oxidative damage. Compared with free DOX, UTMD exhibited improved cytocompatibility in HEK-293 cells.

The Fe-MOF shell functions as a microenvironment-responsive gatekeeper that coordinates controlled drug release with iron-mediated oxidative stress. This integrated design links chemotherapy with ferroptosis-associated mechanisms, improving therapeutic selectivity and mechanistic interpretability.

UTMD represents a microenvironment-activated nanoplatform that enables controlled DOX delivery and ferroptosis-associated oxidative damage. This strategy enhances antitumor efficacy while reducing off-target toxicity, offering potential for improved breast cancer therapy.

The antibody-anticalin fusion protein (Mabcalin) targeting programmed cell death-ligand 1 (PD-L1) and T-cell costimulatory immunoreceptor CD137 (4-1BB) is designed to enhance T-cell reactivity while preventing T-cell inhibition by PD-L1/programmed cell death protein 1 (PD-1) checkpoint blockade. Using positron emission tomography (PET) imaging and ex vivo analysis, we investigated the factors influencing biodistribution, tumor uptake, and the influence of dose and target presence. Methods Murine or human PD-L1-reactive and human 4-1BB reactive Mabcalins (mPD-L1xh4-1BB and hPD-L1xh4-1BB) were generated, radiolabeled with ⁸⁹Zr, and administered to human 4-1BB knock-in (h4-1BB KI) or wild-type (WT) mice bearing PD-L1-positive mouse MC38 tumors. Mice underwent serial PET imaging on days 1, 2, and 4 or on days 2, 4, and 7 post intravenous injection, followed by ex vivo biodistribution. The intratumoral distribution of 2 protein doses of ⁸⁹Zr-radiolabeled mPD-L1xh4-1BB and hPD-L1xh4-1BB was examined using autoradiography on tumor tissue sections. These tumor sections were immunohistochemically stained for PD-L1, CD3, CD8, and 4-1BB to link uptake to target expression levels. Results ⁸⁹Zr-mPD-L1xh4-1BB, able to bind mPD-L1 and h4-1BB in h4-1BB KI mice, predominantly showed specific and rapid dose-dependent lymphoid tissue uptake. The tumor uptake of 200 µg ⁸⁹Zr-mPD-L1xh4-1BB in h4-1BB KI mice was also specific and increased over time. Tumor uptake in this group, where both targets PD-L1 and 4-1BB could be bound, was > 4-fold higher than in the groups that could bind only PD-L1 or 4-1BB. Dual PD-L1 and 4-1BB Mabcalin engagement at a therapeutic dose also resulted in elevated tumor protein expression levels for PD-L1, CD3, and CD8, which were lower when only PD-L1 or 4-1BB was engaged. The lowest expression was observed with the Mabcalin binding non-specifically (P _trend≤0.01 for PD-L1 and CD3, P _trend≤0.05 for CD8). Conclusion The biodistribution of mPD-L1xh4-1BB is specific, dose-dependent, and associated with the elevated target expression resulting from dual PD-L1 and 4-1BB engagement.

Prostate cancer remains a leading cause of cancer-related mortality in men. Although PSMA-directed theranostics have achieved clinical success, heterogeneous expression and therapy-induced downregulation limit their broad applicability. B7-H3 (CD276), which is highly and stably expressed in prostate cancer, represents a promising alternative theranostic target.

A B7-H3 targeted antibody-drug conjugate (ADC) was radiolabeled with [⁸⁹Zr]Zr- for immunoPET imaging and [¹⁷⁷Lu]Lu for radionuclide therapy. In vitro binding specificity, in vivo tumor targeting, biodistribution, therapeutic efficacy, dosimetry, and safety were systematically assessed in prostate cancer xenograft models, with comparisons to radiolabeled antibody, ADC monotherapy, sequential therapy, and vehicle controls.

Histological analysis in prostate cancer patients suggested B7-H3 was consistently and highly expressed in primary and metastatic lesions and remained stable under therapeutic intervention. [⁸⁹Zr]Zr-B7-H3 ADC immunoPET imaging demonstrated high and specific tumor uptake (33.2 ± 1.0 %ID/g at 144 h) and favorable tumor-to-background ratios. Therapeutic studies revealed that [¹⁷⁷Lu]Lu-B7-H3 ADC achieved marked tumor growth inhibition and survival benefit, with comparable efficacy even if reduced the dose of ADC in the treatment system. Integrated [¹⁷⁷Lu]Lu-ADC therapy outperformed radiolabeled antibody, ADC monotherapy, and sequential treatment strategies. No additional organ toxicity was observed compared with ADC alone, and transient hematological changes following [¹⁷⁷Lu]Lu administration were reversible.

The [⁸⁹Zr]Zr-/[¹⁷⁷Lu]Lu-B7-H3 ADC theranostic platform enables accurate imaging, precise tumor targeting, and enhanced antitumor efficacy at reduced ADC doses without increasing systemic toxicity, supporting its translational potential for prostate cancer.

Tumor catalytic therapy represents a promising antitumor approach by inducing ferroptosis and overcoming apoptosis-related resistance mechanisms. Its efficacy is primarily dictated by the extent of membrane lipid peroxidation (LPO). However, tumor cells may evade ferroptosis through metabolic reprogramming that enriches monounsaturated fatty acids (MUFAs) in membrane lipids, thereby diminishing oxidative vulnerability. Hence, strategies that simultaneously enhance catalytic ROS production and reprogram lipid metabolism are required to address this challenge.

To overcome this limitation, a novel Cu-N₃ single-atom nanozyme with edge enrichment (ER-Cu₁SAZyme) was developed, characterized by a hollow porous structure and catalytically active sites concentrated along the edges. This design optimizes atom utilization, increases local electronic density, and lowers the reaction energy barrier, thereby promoting potent intracellular reactive oxygen species (ROS) generation. To further sensitize tumors to ferroptosis, ER-Cu₁SAZyme was combined with sirolimus (Srl), an FDA-approved drug, to create the Srl/ER-Cu₁SAZyme nanomedicine for coordinated catalytic and metabolic regulation.

The Srl/ER-Cu₁SAZyme formulation simultaneously inhibits stearoyl-CoA desaturase 1 (SCD1)-mediated MUFA synthesis and upregulates ACSL4, thereby shifting the membrane lipid composition toward a ferroptosis-sensitive phenotype and enhancing nanozyme-induced LPO. This dual catalytic-metabolic strategy increases ferroptosis susceptibility while reducing metastatic potential linked to excessive membrane fluidity. In tumor-bearing mouse models, Srl/ER-Cu₁SAZyme treatment led to a 33-fold reduction in tumor volume compared to the untreated group, without observable systemic toxicity.

These results highlight the effectiveness of integrating edge-enriched single-atom catalysis with lipid metabolic modulation to enhance ferroptosis-based tumor therapy. The Srl/ER-Cu₁SAZyme nanomedicine offers a safe and highly potent approach for dual catalytic-metabolic regulation in cancer treatment.

The extravasation of anticancer immune cells is a very important issue that must be understood to improve the anticancer effect of chimeric antigen receptor (CAR)-expressing anticancer immune cell therapy. To date, no study has been reported to quantitatively evaluate the degree of extravasation of anticancer immune cells escaping from tumor blood vessels to the tumor microenvironment (TME) at the microscopic level.

In this study, for the first time, using tumor transparency imaging, the extent of extravasation of CAR-NK and NK cells in pancreatic tumors was determined. we used tumor transparency imaging, which preserves intact vasculature, to accurately measure the extravasation and infiltration of established MSLN-CAR-NK-92 cells and unmodified NK-92 cells in an NSG mouse model of pancreatic cancer. Extravasation was quantified by calculating the volume ratio of cells located inside versus outside tumor vessels.

Following intravenous infusion, MSLN-CAR-NK-92 cells showed higher extravasation rates (85.3% vs. 57.4%), penetration depths (185 μm vs. 128 μm), and average extravasated cell counts (7,717 vs. 2,311) compared with NK-92 cells. Further measures of penetration and cytotoxicity also favored MSLN-CAR-NK-92 cells, with CPA50/CPD50 values of 6,887 cells at 88 μm versus 3,509 cells at 45 μm, and CDA50/CDD50 values of 6,350 cells at 102 μm versus 2,023 cells at 48 μm, respectively. These findings highlight the value of extravasation efficiency as a metric for assessing immune cell performance in solid tumors.

Considering these results, the extravasation efficiency of anticancer immune cells can be regarded as a valuable indicator for evaluating the effectiveness of CAR constructs designed for NK cells target pancreatic cancer. In this study, we establish a quantitative extravasation imaging platform for evaluating CAR-NK cell trafficking in pancreatic and cholangiocarcinoma tumor models. This approach provides a structured framework for assessing immune cell delivery and therapeutic distribution within the tumor microenvironment.

PD-1/PD-L1 pathway, a key immune checkpoint, triggers T-cell exhaustion via binding and aiding tumor immune evasion. Although several anti-PD-1/PD-L1 monoclonal antibodies (mAbs) have been granted food and drug administration (FDA) approval, their high cost, poor oral bioavailability, and potential immunogenicity have led to a shift in research toward small molecules. This review summarizes the structure and function of PD-1/PD-L1 and, based on the PD-1/PD-L1 signaling process, focuses on three major classes of related compounds: small molecule inhibitors inducing PD-L1 dimerization or blocking PD-1/PD-L1 binding; PD-L1 degraders (e.g., Proteolysis-targeting chimeras (PROTACs) and Lysosome-targeting chimeras (LYTACs)) via the ubiquitin-proteasome or lysosomal pathway, overcoming membrane protein targeting; and dual-target inhibitors that enhance therapeutic efficacy by exerting synergistic effects. While small molecule drugs have advantages over monoclonal antibodies, including oral administration and reduced immunogenicity, they face drug resistance and toxicity challenges. This review aims to provide insights into the discovery of safe and effective antitumor immunotherapeutic agents.