Postoperative recurrence of glioma remains a major clinical challenge due to the blood-brain barrier and an immunosuppressive tumor microenvironment, necessitating innovative local treatment strategies.

We developed a biomimetic nanoplatform (CaDM) by coating doxorubicin (DOX)-loaded calcium carbonate nanoparticles with a glioma cell membrane. This construct was then integrated with the clinical hemostatic agent Surgiflo to create an in-situ forming depot for localized application into the tumor resection cavity.

The CaDM nanoparticles exhibited excellent acid-responsive degradation, enabling simultaneous release of DOX and Ca²⁺ in the tumor microenvironment. This co-delivery initiated a potent synergistic antitumor effect: DOX induced direct cytotoxicity and immunogenic cell death (ICD), while Ca²⁺ influx triggered calcium overload, mitochondrial damage, and tumor vascular thrombosis. Furthermore, CaCO₃ degradation neutralized the acidic microenvironment, downregulating cathepsin B to reverse immunosuppression. In the postoperative glioma model, CaDM@Surgiflo significantly suppressed tumor recurrence and extended the median survival of mice from 14 days to 40 days. Mechanistic studies revealed that this localized therapy amplifies the ICD cascade through the combined action of DOX and Ca²⁺ overload, which in turn robustly activates dendritic cells and augments the infiltration of cytotoxic T lymphocytes.

This work presents a readily translatable and multifaceted nanomedicine approach that effectively prevents glioma recurrence through synergistic calcium overload and immunomodulation, offering a promising novel strategy for local tumor treatment.

Tumor-derived circulating cell-free DNA (ctDNA) has emerged as a pivotal biomarker for non-invasive cancer diagnosis, treatment monitoring, and prognostic evaluation. However, its inherently low abundance, high fragmentation, and rapid degradation impose stringent requirements on assay sensitivity, specificity, and analytical robustness. Rapid advances in nanotechnology have significantly accelerated progress in ctDNA detection. This review summarizes recent nanotechnology-assisted strategies for ctDNA analysis, including surface-engineered nanomaterials for selective enrichment, nano-enabled signal amplification modalities, and integrated platforms such as CRISPR-based detection, microfluidics and nanopore technologies. We further highlight nanostructure-based approaches for decoding methylation, fragmentation profiles, and multi-omics signatures, focusing on their potential to enhance early cancer detection and real-time therapeutic assessment. Moreover, increasing incorporation of artificial intelligence (AI) which spans nanostructure characterization, aptamer and probe design, multi-omics data integration, and algorithm development is reshaping the landscape of nano-assisted liquid biopsy. Finally, current challenges and future perspectives concerning the clinical translation of nanotechnology-assisted ctDNA detection are presented, emphasizing standardization, biocompatibility, automation, and regulatory readiness. Overall, this review provides a comprehensive outlook on how converging nanotechnology and AI innovations are advancing ctDNA-based precision oncology.

Paclitaxel is a cornerstone of breast cancer treatment, but its efficacy is often limited by low response rates and drug resistance. To address this, we developed MEVs@CuET, a novel therapeutic approach combining cuproptosis-inducing copper(II) complex (CuET) with macrophage-derived extracellular vesicles (MEVs), aiming to enhance paclitaxel's antitumor effects.

The tumor-targeting capability of MEVs@CuET was evaluated through cellular uptake and in vivo distribution studies. In vitro synergy was assessed using the ZIP model, while transcriptome sequencing analyzed gene expression changes. In vivo antitumor activity and immune modulation were examined in breast cancer models, with tumor growth inhibition, apoptosis, and Th17 lymphocyte levels measured.

MEVs@CuET demonstrated efficient tumor targeting and synergistic antiproliferative effects with paclitaxel in vitro (synergy score: 29.37). Transcriptomic analysis revealed significant alterations in immune-related pathways, particularly upregulation of the IL-17 signaling pathway. In vivo, the combination therapy markedly inhibited tumor growth, increased apoptosis, and elevated Th17 cell levels, aligning with the transcriptomic findings.

MEVs@CuET significantly enhances paclitaxel's efficacy by inducing cuproptosis and modulating antitumor immunity, offering a promising strategy to overcome resistance in breast cancer treatment.

Pancreatic ductal adenocarcinoma (PDAC) poses a major challenge due to the lack of effective treatment options and its extremely poor prognosis. Nanodrug delivery systems can improve drug solubility and enable efficient targeted delivery, offering new possibilities for PDAC therapy.

The oncogenic role of KCa3.1 in PDAC was validated through analyses of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases combined with functional assays. To overcome the limitations of conventional therapies, we developed a targeted nanodrug delivery system, TRAM@PPF, based on PLGA nanoparticles modified with polyethylene glycol-folate (PEG₂₀₀₀-FA). This system was prepared by the emulsion-solvent evaporation method to specifically deliver the KCa3.1 channel inhibitor TRAM-34 to PDAC cells. We characterized the nanosystem's physical properties and release profile and evaluated its antitumor efficacy in vitro and in vivo.

The synthesized TRAM@PPF nanoparticles demonstrated uniform size (~142 nm) and excellent stability, with superior cellular uptake compared to non-folate-modified nanoparticles. In vitro, TRAM@PPF showed potent antitumor activity by markedly inhibiting cell proliferation and enhancing apoptosis. Following intravenous administration in pancreatic cancer mouse models, TRAM@PPF significantly inhibited tumor growth, reduced tumor weight, and prolonged survival. Moreover, TRAM@PPF showed excellent biosafety in animal models, suggesting strong potential for further clinical translation in PDAC therapy.

TRAM@PPF preserves folate-mediated tumor-targeting capability while significantly enhancing antitumor activity, offering a promising strategy for targeted therapy of pancreatic cancer.

Poly(ADP-ribose) polymerase (PARP) inhibitors constitute the inaugural targeted therapy shown to enhance the prognosis of individuals with hereditary tumors, initially utilized in the management of patients with germline BRCA1/2-associated breast cancer. With ongoing research, PARP inhibitors (PARPi) are currently under extensive investigation for their applicability across a spectrum of diseases, encompassing oncology, cardiovascular diseases, and cerebrovascular diseases. This narrative review provides a comprehensive synthesis of the biological rationale, existing evidence, recent advancements, and prospective future directions of PARPi in the treatment of cancers, cardiovascular diseases, and cerebrovascular disorders. We provide a comprehensive overview of the recent advancements, advantages, and limitations associated with both clinically approved and investigational PARPi. Beyond their application in oncology, PARPi demonstrate significant potential in other therapeutic domains, including cardiovascular diseases. As our comprehension of the biological functions of PARP and its molecular mechanisms advances, it is anticipated that the therapeutic applications of these inhibitors will broaden considerably. Future research endeavors should prioritize the identification of predictive biomarkers across various diseases and the development of strategies to circumvent drug resistance. Consequently, the integration of fundamental and clinical research on PARPi across diverse diseases is essential to establish a foundational framework for clinical translation.

Gastrointestinal stromal tumor (GIST), the most common gastrointestinal mesenchymal neoplasm, remains poorly understood at the molecular level, limiting precise diagnosis and targeted therapy. This study aimed to systematically identify key GIST-associated genes through multiomic integration and experimental validation. We analyzed three GIST transcriptomic datasets from GEO, corrected batch effects via surrogate variable analysis (SVA), and identified 61 differentially expressed genes (DEGs) using limma. Weighted gene co-expression network analysis (WGCNA) highlighted progression-related modules, which were refined using random forests and LASSO regression to prioritize C3 and complement factor D (CFD), both of which showed robust diagnostic performance (AUC: 0.928 for C3; 0.955 for CFD). Experimental validation confirmed C3/CFD downregulation in GIST tissues, correlating with advanced stage and poor survival. Functional assays demonstrated their tumor-suppressive roles, inhibiting GIST cell proliferation, colony formation, and migration. CIBERSORT analysis linked C3/CFD to altered immune infiltration, while ssGSEA/GSEA implicated their involvement in lipid metabolism and oxidative phosphorylation. These findings establish C3 and CFD as critical tumor-suppressive biomarkers that modulate the immune response and reprogram metabolism, offering new avenues for GIST diagnosis and therapy.

This work describes the design, synthesis, and anticancer evaluation of a new acridine hybrid (ACNP). ACNP showed cytotoxic effect with IC₅₀ values of 4.3 and 10 μg/mL against MCF-7 and MDA-MB 231; respectively, versus CC₅₀ value of 439.72 μg/mL of normal lung fibroblast cells (WI-38 cells) with high selectivity index (SI) of 102.2 and 43.9 for MCF-7 and MDA-MB 231 of cancer cells respectively. ACNP showed a cytotoxic synergetic effect when combined with paclitaxel in MDA-MB 231 and MCF-7 cell lines. A significant down regulation of PI3K, mTOR and AKT was demonstrated in cells treated with paclitaxel or ACNP as single therapy with minimal expression in cells treated with combination of both. ACNP treated cells recorded an increase in protein expression level of Caspase-3, Caspase-9 while Ki67 showed a declined expression in MDA-MB 231 and MCF-7 cell lines. Molecular docking investigation was performed on PI3K and Caspase-3 to predict the possible binding modes of the acridine tricyclic skeleton with the molecular targets. The ADME study revealed that ACNP has high GI absorption and blood brain barrier although oral bioavailability was poor. These results suggested that ACNP maybe a promising candidate for further preclinical development.

Lung cancer continues to be among the most fatal malignancies globally and exhibits a complex interplay with tuberculosis (TB). These conditions share several pathogenic pathways, notably involving apoptosis and autophagy, which play critical roles in disease progression and therapeutic responsiveness. MicroRNAs (miRNAs) function as pivotal post-transcriptional regulators, with miR-34a and miR-182 increasingly recognized as key modulators. Beyond their established roles in tumor development and host-pathogen interactions, these miRNAs influence diagnostic accuracy and therapeutic approaches in both lung cancer and TB METHODS: To investigate miRNA-driven regulatory mechanisms, A549 lung adenocarcinoma cells and THP-1 monocytic cells were transfected with vectors designed to overexpress miR-34a and miR-182. Apoptotic and autophagic processes were quantitatively assessed using high-resolution flow cytometry alongside functional validation assays. Additionally, the expression of key apoptotic and autophagy-related genes was analyzed to characterize downstream molecular effects resulting from miRNA modulation.

Quantitative real-time PCR analysis demonstrated that miR-34a upregulated Bax while downregulating Bcl-2, leading to a pronounced increase in the Bax/Bcl-2 ratio. In contrast, miR-182 enhanced the expression of both Bax and Bcl-2, yet still facilitated apoptosis through an overall elevation of the Bax/Bcl-2 ratio. Within the autophagy-related signaling network, miR-34a exerted a suppressive effect on IL6, FOXO3, and TNFα expression, whereas miR-182 promoted the expression of genes associated with autophagic activity. These molecular findings were corroborated by flow cytometry, which revealed increased apoptotic activity accompanied by diminished autophagy. Collectively, the data indicate distinct yet complementary regulatory functions of miR-34a and miR-182 in determining cellular fate.

miR-34a and miR-182 exert significant regulatory effects on apoptotic and autophagic pathways in the context of lung cancer and tuberculosis. Their differentiated but coordinated actions highlight their potential utility as diagnostic biomarkers and therapeutic modulators. These findings suggest promising translational implications for the precision management of both infectious and malignant pulmonary disorders.

Ovarian cancer (OC) presents a formidable challenge in terms of early detection due to its subtle symptoms, often leading to diagnosis at advanced stages of the disease. Despite therapeutic advancements, survival rates exhibit limited improvement. This study delves into long non-coding RNAs (lncRNAs) associated with cuproptosis, aiming to anticipate the prognosis of OC and assess its immune status. The findings of this study provide a framework for enhancing the treatment of OC. RNA-seq and clinicopathological data of 379 TCGA-OC samples were retrieved from UCSC Xena. After extracting mRNAs/lncRNAs and screening CRLs via Pearson's analysis, a prognostic model was built and validated. Subgroup, PCA, GO/KEGG, immune infiltration, TMB, and drug sensitivity analyzes were conducted for evaluation. A prognostic ensemble, consisting of eight lncRNAs namely AC104820.2, EPB41L4A-AS1, LINC00996, RP11-110I1.6, RP11-367G6.3, RP11-443B7.3, RP11-4O1.2, and RP11-76E17.3, was effectively formulated. Independent prognostic factors for OC were identified through Cox analysis, with age and risk score emerging as noteworthy contributors. The prognostic signature demonstrated robust efficacy in the anticipation of 1-year, 3-year, and 5-year overall survival rates. Notably, individuals with low-risk OC manifested distinctive tumor immune microenvironments and exhibited an elevated tumor mutational burden. Furthermore, this low-risk cohort displayed heightened responsiveness to diverse therapeutic agents in comparison to their high-risk counterparts. Collectively, the comprehensive analysis of cuproptosis-associated lncRNAs serves a dual purpose in prognostication and elucidation of the immune microenvironment and therapeutic responsiveness in OC.

Gastric cancer (GC) develops through a sequence from chronic gastritis to intestinal metaplasia (IM) and carcinoma, with Helicobacter pylori (HP) as a key driver; however, the molecular mediators linking inflammation to malignant transformation remain unclear. We integrated single-cell RNA sequencing and spatial transcriptomics of gastric mucosal samples from atrophic gastritis, IM, and GC, including HP positive (+) and HP negative (-) cases, to map cellular heterogeneity, differentiation trajectories, and pathway activities. Our analyses revealed that IM epithelium represents a transitional state between normal and malignant epithelial lineages, characterized by enhanced WNT signaling that promotes neoplastic progression, whereas H. pylori-associated inflammation activates NF-κB signaling. Across analysis, UPP1 was consistently upregulated in malignant and H. pylori-positive epithelium, increasing along pseudotime toward cancer-like states. Spatial mapping and organoid experiments confirmed that UPP1-high cells had higher intestinal differentiation scores, while UPP1 knockout promoted IM-like morphology in WNT-depleted cultures. Clinically, UPP1 was elevated in GC versus normal tissues, correlated with advanced TNM stage, predicted poor survival, and was higher in HP⁺ tissues. Knockdown in GC cell lines reduced clonogenicity and migration. Collectively, these findings identify UPP1 as a key regulator of epithelial reprogramming and IM, linking H. pylori-driven inflammation with WNT-mediated differentiation, and highlight its potential as a prognostic biomarker and therapeutic target in GC.