Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality, and the development of safer and more effective delivery systems remains an important goal. Exosome-like nanoparticles (ELNs) from edible and medicinal sources, including medicinal plants and mammalian milk, have shown gastrointestinal stability, systemic absorption, hepatic enrichment, or therapeutic activity in selected preclinical models. However, these properties are source-, preparation-, route-, and model-dependent and should not be generalized to all edible ELNs. This structured narrative review critically evaluates evidence relevant to HCC by distinguishing: (i) direct anti-HCC studies; (ii) liver disease and gut-liver axis studies indirectly relevant to HCC prevention; and (iii) non-HCC cancer studies that provide mechanistic or engineering insights. We discuss apoptosis, cell-cycle regulation, ferroptosis, immune and gut-liver axis modulation, as well as biomimetic targeting, stimuli-responsive delivery, and theranostic applications. Particular attention is paid to context-dependent pro-metastatic signals reported for bovine milk-derived extracellular vesicles, critical quality attributes, scalable manufacturing, food-drug interactions, and regulatory uncertainty. Current evidence supports edible ELNs as promising but early-stage preclinical platforms; clinical translation for HCC will require standardized characterization, clinically relevant disease models, reproducible manufacturing, and prospective safety evaluation.
Taurine (TAU) has context-dependent roles in gastric cancer. Although exogenous TAU may promote tumor cell growth in vitro, increasing local TAU availability within the tumor microenvironment may support CD8⁺ T-cell-associated antitumor immunity. Here, we developed hyaluronic acid-modified taurine-polydopamine nanoparticles (H/T/PDA) for combined photothermal-immunotherapy of gastric cancer. PDA served as both a TAU carrier and photothermal agent, while HA modification was designed to improve tumor-associated accumulation. H/T/PDA showed good colloidal stability, ROS/pH/light-responsive TAU release, and efficient photothermal conversion under 808 nm laser irradiation. In vitro, H/T/PDA induced photothermal cytotoxicity against gastric cancer cells and promoted ICD-related CRT exposure. TAU-containing formulations enhanced IFN-γ and IL-2 secretion in primary CD8⁺ T cells, while MFC/CD8⁺ T-cell co-culture experiments suggested a net antitumor effect in an immune-cell-containing system. Mechanistic assays further supported SLC6A6-related TAU uptake and increased local TAU availability after H/T/PDA treatment. In MFC tumor-bearing 615 mice, H/T/PDA combined with NIR irradiation produced the strongest tumor suppression among the tested groups and was associated with increased tumor cytokine levels. Preliminary biosafety evaluation showed no obvious hematological, biochemical, or major organ toxicity during the treatment period. These findings suggest that H/T/PDA may serve as a potential nanoplatform for integrating TAU replenishment, photothermal therapy, and immune-associated tumor microenvironment modulation.
Hepatocellular carcinoma (HCC) is still one of the most morbid cancers in the world, mainly due to delayed diagnosis resulting from significant molecular heterogeneity and rapid acquisition of resistance to treatment. Definitive therapies such as surgery and locoregional techniques have been successful in a subset of patients, yet systemic chemotherapy and overall FDA-approved targeted agents offer only modest improvement for advanced disease. siRNA-based therapy provides a targeted silencing mechanism for the selective downregulation of oncogenic drivers and resistance-associated pathways. However, the clinical translation of siRNA therapeutics is critically contingent upon safe and effective delivery platforms that are clinically viable. Lipid-based nanomedicines are thus far among the most effective carriers for siRNA delivery because of their excellent biocompatibility, natural affinity with the liver, easy scalable production and clinical feasibility. This review provides critical insight into major molecular pathways involved in HCC development, such as angiogenic signaling, growth factor cascades and survival and metabolic networks, which offer potential targets for pathway-specific siRNA intervention. The physicochemical characteristics, delivery strategies, formulation techniques, mechanisms of endosomal escape and fine-tuning of the transfection efficiency of lipid-based siRNA carriers are comprehensively reviewed. In addition, prominent preclinical lipid-based nanotechnologies designed to target major oncogenes and survival mediators are outlined in conjunction with translation implications, including production cost, scalability, and regulatory readiness. The current status of the clinical development of lipid-based siRNA therapeutics for HCC is also discussed, with a focus on safety and the constraints associated with monotherapy. The role that artificial intelligence plays in siRNA sequence optimization, biodistribution prediction and formulation development is also described. Finally, challenges and perspectives are discussed, including multipathway silencing tactics, linkages with immunotherapy, and personalized nanomedicine to increase therapeutic effectiveness in HCC.
Metastasis remains the leading cause of cancer-related mortality, yet the metastatic cascade is initiated long before circulating tumor cells reach distant organs. Central to this early phase is the premetastatic niche (PMN), a dynamic and tumor-conditioned microenvironment in which vascular, stromal, metabolic, and immune compartments are progressively reprogrammed to support metastatic seeding. Among the mechanisms that orchestrate this process, platelet–neutrophil crosstalk has emerged as a critical thromboinflammatory axis linking hemostatic activation to innate immune remodeling and niche permissiveness. Tumor-derived signals activate platelets, which in turn engage neutrophils through key adhesive pathways, including P-selectin–PSGL-1 and GPIbα–Mac-1, thereby promoting platelet–neutrophil aggregation, endothelial dysfunction, microthrombus formation, and local inflammatory amplification. This interaction is further reinforced by neutrophil extracellular traps (NETs), which function as extracellular scaffolds that trap circulating tumor cells, remodel the extracellular matrix, expose pro-adhesive ligands, and protect malignant cells from immune surveillance. Together, platelet activation, neutrophil reprogramming, and NETosis establish a self-amplifying immunothrombotic niche that facilitates vascular arrest, tumor-cell survival, and metastatic colonization. Despite this mechanistic progress, important translational gaps remain, including limited human validation, the absence of robust biomarkers for PMN activity, and an incomplete understanding of species-specific differences in platelet–neutrophil biology. This review synthesizes current evidence on the molecular basis of platelet–neutrophil cooperation in PMN formation and discusses emerging anti-metastatic strategies, with particular emphasis on anti-adhesion approaches, anti-NET interventions, and stimuli-responsive nanotherapeutic platforms designed to deliver anti-platelet, anti-inflammatory, and anti-NET agents to nascent metastatic niches. Collectively, these data support the platelet–neutrophil–NET axis as a compelling therapeutic and biomarker-focused target for early metastasis interception.
This globally first systematic review and meta-analysis quantitatively evaluates the efficacy, safety, and dose–response relationships of gold (Au) nanoparticle-mediated photothermal therapy (PTT). A systematic search was conducted across four major databases for preclinical studies published between 2015 and 2025, adhering to PRISMA guidelines (PROSPERO registration: CRD420251250129). Random-effects meta-analysis was employed to pool effect sizes for tumor growth inhibition and temperature elevation. Furthermore, a dose–response meta-regression and subgroup analysis were performed to elucidate the relationship between nanoparticle concentration, radiation intensity and therapeutic efficacy. The OHAT and SYRCLE tools were used to rate the quality of the included studies. Ultimately, 162 (113 in-vitro and 72 in-vivo) and 64 studies satisfied the inclusion criteria for the systematic review and quantitative meta-analysis, respectively. The best photothermal conditions were a wavelength of 808 nm, a laser intensity of 0.5–3.0 W/cm2, and an irradiation time of 5–10 min. Also, among nanostructure morphologies, Au nanorods (optimal size 80 nm) demonstrated superior photothermal efficiency. The pooled analysis of the two primary variables revealed a strong therapeutic response, characterized by a mean intra-tumoral temperature elevation of 15.30 °C (95
Magnetic hyperthermia (MHT) is a cancer treatment modality that employs magnetic nanoparticles (MNPs) to generate localized heat upon exposure to an alternating magnetic field (AMF), typically operating within the 100 kHz–1 MHz frequency range. Recent advances have identified trapezoidal pulsed AMFs (TPAMFs) as a compelling alternative to traditional sinusoidal waveforms, demonstrating enhanced heating performance and more efficient thermal responses in nanoparticle-mediated MHT. The objective of this study is to evaluate the therapeutic efficacy of TPAMF-driven MHT relative to the conventional sinusoidal approach using an in vivo murine glioblastoma model. It is important to note that neither MNP administration nor AMF exposure alone is sufficient to slow tumor progression or reduce the final tumor size. In contrast, treatment with non-sinusoidal waveforms, particularly trapezoidal pulses, significantly enhanced tumor ablation in vivo. These findings demonstrate that waveform optimization can markedly improve the therapeutic performance of MHT and support the development of more effective magnetic hyperthermia-based cancer therapies.
Cancer remains a critical global health challenge, leading to millions of deaths worldwide due to its rapid progression and complex resistance mechanisms. However, conventional therapeutic modalities are frequently constrained by tumor hypoxia, heterogeneity, therapeutic resistance, and off-target toxicity, emphasizing the necessity for robust and precise therapeutic approaches. Development of nanozyme-based approaches has provided innovative avenues for catalytic cancer therapy. However, the therapeutic capability of traditional approaches is often hindered by low catalytic efficiency and minimal production of reactive oxygen species (ROS) within the tumor microenvironment (TME). Consequently, piezoelectric nanozymes have emerged as a next-generation category of multifunctional nanocatalysts that integrate enzyme-mimicking catalytic activity with piezoelectric energy conversion, enabling effective and accurate tumor treatment under external mechanical stimulation. Piezoelectric polarization-mediated enhanced charge separation facilitates catalytic amplification, ROS generation, enhanced electron (e−) transfer, and redox regulation, thereby addressing major constraints associated with conventional therapeutic techniques. This review comprehensively describes the charge-generating properties of piezoelectric materials with enzyme-mimicking catalytic activity, catalytic mechanisms, design strategies and current advancements in piezoelectric nanozyme-driven cancer therapy. Sonodynamic therapy (SDT), ferroptosis therapy, radiocatalytic therapy(RCT), starvation therapy (ST), piezocatalytic therapy(PCT), chemodynamic therapy (CDT), immunotherapy, and their synergistic combinations are all discussed in detail. Piezoelectric nanozymes offer a versatile platform for multimodal cancer therapy and represent a promising paradigm for developing strategies for precise, non-invasive cancer therapy through localized ROS generation and modulation of the TME.
The prevalence of head and neck cancer is increasing, raising concerns regarding the rate of recovery, recurrence, and aggressive surgical approaches that have negatively impacted patient welfare. In this context, nanomedicine has emerged as a promising alternative, offering a progressive therapeutic approach with enhanced efficacy and improved outcomes. This systematic review aims to evaluate studies employing nanomaterials as carriers for chemotherapeutic agents, providing evidence-based insights and synthesizing the available data into a comprehensive analysis. In this systematic review, 14 preclinical original research articles were included using animal models and subjected to experimental methods quality evaluation. The findings demonstrated widespread use of nanomaterial-based chemotherapeutic delivery systems, with several studies reporting improved antitumor outcomes, reduced toxicity, and decreased metastatic potential compared with conventional approaches. However, these findings were interpreted cautiously, as differences in dosing strategies across studies may have influenced treatment comparisons. Overall, the available evidence provides valuable insight into the current state of nanomaterial-based chemotherapeutic delivery and its potential translation into a viable strategy for addressing multidrug-resistant carcinomas, while enabling dose reduction and ultimately improving patient outcomes and welfare. Nevertheless, studies investigating alternative nanomedicine delivery routes remains limited. This highly innovative approach warrants urgent investigation, with particular focus on safety and efficacy of this new form of therapy, to better understand its potential as an alternative therapeutic strategy.
The therapeutic efficacy of cisplatin is limited by systemic toxicity, acquired resistance, and poor cancer cell specificity. To address these limitations, we developed solid lipid nanocarriers for the co-delivery of nisin and cisplatin (Nis + Cis-SLNs). The developed SLNs exhibited monodisperse spherical morphology, high encapsulation efficiency and sustained release. The therapeutic potential of Nis + Cis-SLNs was evaluated against epithelial malignancies using human epidermoid carcinoma (A431) and breast adenocarcinoma (MCF-7) cells. The nanocarriers demonstrated enhanced cytotoxicity compared to free nisin and cisplatin by synergistically targeting proliferation, apoptosis, and reactive oxygen species generation. Nis + Cis-SLNs triggered an intrinsic apoptotic response by upregulation of caspase-3, Bax, and suppression of Bcl-2. Beyond direct cytotoxicity, conditioned media derived from Nis + Cis-SLNs treated tumor cells were associated with reduced M2 macrophage polarization, suggesting a possible role in immunomodulation of the tumor microenvironment. Collectively, these findings highlight the potential of Nis + Cis-SLNs as a promising co-delivery strategy to enhance cisplatin efficacy at reduced doses, potentially improving therapeutic outcomes.
Plant-derived exosome-like nanoparticles (PELNs) transport multi-component molecular cargos with cross-kingdom regulatory potential and have emerged as a promising class of cancer nanomedicines. A persistent bottleneck, however, is causally linking individual cargo species to in vivo antitumor mechanisms, because the simultaneous presence of proteins, miRNAs, and metabolites obscures which cargo drives which downstream phenotype. We isolated Houttuynia cordata aerial-herbage exosome-like nanoparticles (aHELNs) and underground-root nanoparticles (uHELNs) by differential and ultracentrifugation. We evaluated aHELN antitumor activity in A549, H1975, and H520 non-small cell lung cancer (NSCLC) cell lines and in a subcutaneous A549 xenograft model by oral gavage (10, 20, or 30 mg protein/kg every other day for 18 days). Cargo was profiled by label-free proteomics, small RNA sequencing, and headspace SPME-GC-MS metabolomics, and tumor tissue was profiled by 4D-DIA proteomics. We developed Multi-omics Convergence Screening (MOCS), a transparent, rule-based prioritization strategy that anchors predicted miRNA- and metabolite-target relationships to in vivo tumor differentially expressed proteins from the same treatment cohort. Selected MOCS nominations were evaluated by dual-luciferase reporter assays, an 8-gene RT-qPCR panel including a MOCS-negative control (PRKAR1B), molecular docking, molecular dynamics (MD), a drug affinity-responsive target stability (DARTS) assay, and Western blotting, and were anchored to The Cancer Genome Atlas lung adenocarcinoma cohort (TCGA-LUAD; n = 517 tumor, 58 normal, 57 matched pairs) and MSigDB Hallmark gene-set enrichment analysis (GSEA). aHELNs produced dose-dependent tumor suppression without overt organ toxicity. MOCS resolved two complementary candidate modules: a miRNA-dominant module comprising TRPC7, ABL2, SENP1, and CXCL14 and a metabolite-associated module comprising SHBG, ADH1C, and FABP3. Dual-luciferase reporters confirmed seed-dependent 3′UTR suppression for hco-miR166e-3p targeting TRPC7 and for hco-miR447a-3p targeting ABL2 (WT+mimic vs. WT + NC fold = 0.73, t = -16.51, P < .001, Cohen’s d = -10.44). An 8-gene RT-qPCR panel supported MOCS-predicted transcriptional directionality; SENP1, CXCL14, ADH1C, and FABP3 remained expression-supported exploratory candidates, while the MOCS-negative control PRKAR1B remained unchanged (F = 0.83, P = .512). Computational modeling placed β-caryophyllene within the SHBG ligand pocket (docking energy = −8.526 kcal/mol; stable MD RMSD), while DARTS showed concentration-dependent protection of SHBG from proteinase K digestion and Western blotting confirmed concentration-dependent SHBG accumulation. In TCGA-LUAD, TRPC7 and SHBG were both reduced in tumor versus normal (Mann-Whitney P < .001 for both); a combined logistic classifier achieved AUC = 0.774 (95
Biogenic platinum nanozymes (PtNZs) represent a distinct class of catalytic nanomaterials in which nanoparticle formation and biological functionalization occur concurrently, yielding hybrid systems governed by inseparable core-corona interactions. Despite rapid growth in this field, the absence of a unifying design framework has limited mechanistic understanding, cross-study comparability, and rational optimization for cancer theranostic applications. This review introduces the concept of core-corona catalytic coupling as a governing principle that defines nanozyme behavior across biological contexts, with particular emphasis on the tumor microenvironment. Moving beyond descriptive synthesis-focused reviews, we establish a structure-activity framework that links physicochemical parameters of the platinum core (size, morphology, electronic structure) with biomolecular corona composition and dynamic microenvironmental conditions. From this analysis, we derive seven principles that collectively determine catalytic performance, enzyme-mimetic activity profiles, and therapeutic function. We demonstrate that high-performing PtNZ systems consistently converge on three coupled parameters: ultrasmall particle dimensions (< 10 nm), biomolecule-rich corona, and catalytic activity matched to tumor biochemical environments. We elucidate how catalytic switching between pro-oxidant and antioxidant modes emerges from microenvironment-dependent modulation of core-corona interactions. By integrating evidence across synthesis strategies, catalytic mechanisms, and biomedical applications, we reframe biogenic PtNZ as designable catalytic systems rather than empirically optimized materials. We identify key translational bottlenecks, including batch variability, incomplete corona characterization, and regulatory uncertainty, and propose solutions leveraging synthetic biology and machine learning. We also highlight emerging anticoagulant activity in biogenic PtNZ as an underexplored therapeutic niche with wound healing relevance. This core-corona structure-activity framework establishes a foundation for rational design, standardized evaluations, and accelerated clinical translation of biogenic platinum nanozymes in cancer nanomedicine. Biogenic synthesis co-designs platinum nanozyme cores and biomolecular corona in a single step, eliminating post-synthetic functionalization. Core-corona architecture dictates enzyme-mimetic activity (POD, CAT, SOD, OXD) and reactive oxygen species (ROS) modulation critical for cancer catalytic therapy. A seven-principle structure-activity framework links physicochemical parameters to functional outcomes across cancer theranostics and companion biomedical applications. Cancer theranostic performance converges on three coupled parameters: ultrasmall size, biomolecule-rich corona, and activity matched to the tumor microenvironment. Critical translational gaps, including reproducibility, corona characterization, and immunogenicity, are identified alongside solutions via synthetic biology and machine learning. Machine learning and synthetic biology offer avenues for rational design and predictable catalytic performance.
Over the past two decades, research on small interfering RNA (siRNA)-based cancer therapies has advanced substantially; however, a comprehensive, data-driven evaluation of its translational trajectory remains limited. We retrieved 27,236 publications from the Web of Science Core Collection (2002–2024) and conducted bibliometric analyses using Bibliometrix-Biblioshiny, VOSviewer, and CiteSpace. Global output showed an average annual growth rate of 23.8
Enzalutamide (ENZ) resistance has emerged as a critical therapeutic hurdle in advanced prostate cancer (PCa) management. This study aims to investigate the potential of ultrasound-guided nanobubble-mediated co-delivery of small interfering RNA targeting fibroblast growth factor receptor 1 (siFGFR1) and ENZ to overcome ENZ resistance in PCa. The nanobubbles (PFP-ENZ@siRNA-NBs-RGD) were characterized for particle size, zeta potential, and morphology. Their biocompatibility was confirmed via hemolysis assays. In vitro, selective targeting of PCa cells was observed, and the system exhibited minimal toxicity to normal cells while effectively inhibiting ENZ-resistant PCa. Under ultrasound, ENZ and siFGFR1 downregulated AR/PSA, p-PI3K/p-Akt/p-mTOR and P-gp, and modulated apoptotic-related proteins (Caspase-3/Bax upregulated, Bcl-2 downregulated). Additionally, apoptosis rates were significantly increased. In vivo, tumor growth was reduced, with concurrent suppression of p-PI3K/p-Akt/p-mTOR, P-gp downregulation, and apoptotic-related protein modulation in tumor tissues, validating in vitro mechanisms. Moreover, no adverse effects were observed. These findings suggest that the ultrasound-guided co-delivery of siFGFR1 and ENZ via nanobubbles represents a promising strategy to combat ENZ-resistant prostate cancer.
Retinoblastoma is very challenging because it can cause blindness and has strong metastatic, life-threatening potential. Prompt treatments transferred to the tumor site are impaired by several barriers, such as anatomical, physiological, biochemical, and other complications. Liposomes represent the most extensively utilized class of nanocarriers for delivering both hydrophobic and hydrophilic therapeutic and diagnostic agents, owing to their exceptional biocompatibility, biodegradability, and minimal immunogenicity. Usual liposomes have weak performance in crossing ocular barriers and delivering their cargo. Engineered liposomes offer controlled distribution and versatile surface modification capabilities, enabling targeted and sustained release of drugs. Over time, liposomal formulations have evolved through four distinct generations, transitioning from conventional vesicles to sophisticated, stimulus-responsive, and actively targeted systems. Several liposome-based drug delivery platforms have received clinical approval for the treatment of cancer and infectious diseases, with numerous others currently undergoing evaluation in advanced clinical trials. This review provides a comprehensive overview of various liposome types, their classifications, lipid compositions, cellular uptake mechanisms, and clinical translational aspects specific to retinoblastoma therapy. It further addresses existing limitations and explores promising avenues for advancing liposome-mediated drug delivery in the treatment of ocular cancer.
Smart drug delivery systems (SDDS) have the capability to respond to the unique conditions of the tumor microenvironment (TME) for improved anticancer efficacy and reduced toxicity to normal tissues. The TME is characterized by various physicochemical changes such as altered redox potential, acidic pH, hyperthermia, and the abnormal expression of various tumor- associated antigens andenzymes have drawn significant interest in the use of stimulus-responsive nanocarriers for cancer theranostics. The stimuli -responsive nanocarriers are developed to respond to external (ultrasound, light, magnetic field, thermal, etc.) as well as to the internal stimuli (pH, hypoxia, redox potential and enzymes, etc.) for effective delivery of therapeutic and imaging agents to the targeted sites. Smart nanocarriers encapsulated drug delivery systems such as liposomes, dendrimers, micelles, quantum dots, mesoporous silica nanoparticles, carbon nanotubes, gold nanoparticles, etc. are under development for tackling cancer progression effectively and are currently undergoing clinical evaluation to assess their safety and efficacy against various cancers. The article highlights the recent advances in stimuli -responsive smart nanocarriers, with particular emphasis on their integration into a unified theranostic approach for both cancer diagnosis and treatment.
Macrophages are a major component of the immune infiltrate in brain tumors and play a crucial role in shaping the tumor microenvironment. Their pronounced plasticity makes them attractive targets for therapeutic reprogramming, particularly to enhance antitumor phagocytic activity. Among key immunoregulatory receptors, CSF1R and PD-L1, which are expressed on macrophages, contribute to immunosuppression and tumor progression. Liposomes are well-established multivalent platforms that can present high densities of targeting ligands, increasing binding avidity and specificity; however, they can undergo rapid immune clearance, which limits their utility in brain tumor settings. In contrast, exosomes are biologically derived nanoparticles with inherent biocompatibility and immune-evasive properties; when fused with liposome membranes, they can endow synthetic vesicles with a more physiological surface and enhance circulation. To explore these complementary features in a reductionist in vitro setting, an exosome–liposome hybrid nanoparticle platform was engineered and functionalized with αCSF1R antibodies and αPD‑L1 nanobodies to target tumor‑associated macrophages differentiated from THP-1 monocytes in the presence of glioblastoma- and medulloblastoma‑derived tumor‑conditioned media. Hybrids exhibited 22
Abstract Background Hepatocellular carcinoma (HCC) has one of the highest mortality rates among solid cancers and remains a major global health burden. Its incidence has been rising over the past 20 years and is projected to continue increasing in the coming decades. Current global models predict that the burden of liver cancer, including HCC, may nearly double by 2050 if present trends continue, driven by viral hepatitis, metabolic dysfunction-associated steatotic liver disease, and alcohol-related liver disease. Despite advances in diagnosis and therapy, outcomes remain poor due to late detection and limited effective treatment options. Methods This study was designed in three arms, the first was to evaluate the safety of sulfur extract nanoparticles (SEx-NP) on the liver, and then the second was studying the ability of SEx-NP to prohibit the occurrence of HCC, while the third was evaluating the therapeutic effect of SEx-NP on HCC. Results Acute toxicity study was done using 1800 mg/kg of SEx-NP which was the maximum soluble dose, it was safe. Sub-chronic toxicity study proved that 180 mg/kg of SEx-NP was safe. Preventive and therapeutic efficacy studies were done, animal groups were: Negative control, positive control received diethyl-nitrosamine (DENA) (200 mg/kg), and carbon tetrachloride (CCL 4 ) 9% (0.5 ml/kg) intraperitoneally, to induce a rat model of HCC, preventive groups were given SEx-NP orally (90 and 180 mg/kg), together with DENA and CCL 4 for 3 and 6 months, therapeutic group was given SEx-NP orally (90 mg/kg) for 1 month, after induction of HCC. Biochemical parameters measured in sera were: GPT, GOT, MDA, IL-β 6 , TNF-α, α-fetoprotein, ova albumin, TGF-β 1 and pyruvate kinase levels in addition to histopathologic and immuno-histochemical examination of hepatic tissues. SEx-NP reduced GPT, GOT, MDA, IL-β 6 , TNF-α, α-fetoprotein, ova albumin, TGF-β 1 and pyruvate kinase with better effect in the therapeutic study, it also improved the hepatic histopathologic pictures. Conclusions Our results demonstrate the potential inhibitory effect of SEx-NP tumor on growth during early HCC stages, reinforcing its prophylactic promise in liver cancer prevention and liver health support. Finally, we can conclude that SEx-NP is a promising anti-neoplastic supplement.
Luteolin, a naturally occurring flavonoid abundant in vegetables and medicinal plants, is increasingly recognized for its anticancer potential through pleiotropic effects on cellular signaling and gene expression. Recent research highlights its capacity to modulate multiple oncogenic pathways, regulate microRNA (miRNA) networks, and improve therapeutic efficacy when delivered via engineered nanocomposites. This narrative review critically evaluates current evidence on the molecular mechanisms by which luteolin interferes with cancer hallmarks. Particular focus is given to its influence on intracellular signaling cascades, miRNA regulation, and the development of nanocarrier-based delivery strategies. Literature was retrieved from PubMed, Scopus, and Web of Science up to October 2025, with selection based on relevance to cancer-related signaling pathways, miRNA modulation, and nanomedicine. Key mechanistic insights and experimental findings are synthesized into structured tables and pathway illustrations. Luteolin was found to suppress cancer progression through modulation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Janus kinase/signal transducer and activator of transcription (JAK/STAT), Wnt/β-catenin, and Notch signaling pathways, and to restore apoptosis sensitivity through tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated mechanisms. It also regulates oncogenic and tumor-suppressive miRNAs including miR-34a, miR-203, and let-7c. Moreover, folic acid-conjugated oxidized alpha-cyclodextrin (FA-Oxi-αCD) nanoparticle formulations significantly enhance luteolin’s bioavailability and tumor-specific delivery. In summary, luteolin represents a promising multi-targeted anticancer agent. Its rational incorporation into nanocomposite drug delivery systems may overcome existing clinical limitations and warrants further translational and clinical investigation.
Proton boron capture therapy (PBCT), based on proton-boron fusion reactions (11B + p →3α + 8.7 MeV), has the potential to enhance the biological effectiveness of proton therapy. To achieve this potential, the efficient delivery of enough 11B to cancer cells will be paramount. This study demonstrates a newly developed method of poor solvent–mediated spontaneous assembly of polymeric micelles with entrapped o-carborane, in which ethanol is a good solvent for the payload o-carborane but a poor solvent for the hydrophobic segment poly(ε-caprolactone) in this amphiphilic block copolymer. This method provided smaller polymeric micelles compared to use of tetrahydrofuran, a good solvent for the amphiphilic block copolymer, as the sole solvent for both payload and copolymer. The prepared nanoscale formulation enabled the boron-rich cage compound o-carborane to be effectively delivered to tumor cells, and its enhancement of the biological effectiveness of proton therapy was preliminarily validated in a pancreatic ductal adenocarcinoma cell line, MiaPaCa-2, by survival assays and DNA damage assessment. The 111In-labeled congener was also successfully prepared and used in biodistribution assays in normal mice, opening the way to further studies on image-guided PBCT in preclinical animal models.
Reactive oxygen species play a key and paradoxical role in tumor progression biology. At physiological levels, ROS act as important signaling molecules that control growth, survival, and metabolism. This redox balance becomes disrupted in cancer, leading to chronically elevated ROS levels that further promote genetic instability, metabolic changes, angiogenesis, spread, and resistance to chemotherapy or radiotherapy. Under prolonged oxidative stress, tumor cells strengthen antioxidant defense systems to avoid lethal oxidative damage. Conventional antioxidant approaches have shown limited clinical success. Indiscriminate ROS scavenging can disrupt essential redox-dependent signaling pathways and may compromise the effectiveness of ROS-based anticancer therapies. Redox-modulating nanoplatforms have emerged as a promising alternative by enabling precise, context-dependent modulation of redox homeostasis rather than global ROS suppression. With their tunable physical qualities, catalytic redox activity, and tumor-targeting potential, redox-modulating nanoplatforms can serve as dynamic redox buffers that specifically respond to the oxidative, acidic, and hypoxic tumor microenvironment without damaging the normal cells. These nano-systems regulate redox-sensitive signaling pathways, control mitochondrial ROS production, and influence ferroptosis and tumor microenvironment dynamics. Collectively, these effects improve therapeutic efficacy while reducing systemic toxicity. This review highlights current progress in nano-antioxidant design, processes of redox regulation, medicinal uses, and translational hurdles, showing their possible role in precision redox-based cancer treatment.
