In this study, we developed a tumor-target biotinylated cytarabine (Ara-C) prodrug linked through a disulfide bond (Bio-SS-Ara). To enhance its delivery, Bio-SS-Ara was found to be able to self-assemble into uniform nanoparticles (BSSA NPs) with an average particle size of 230 nm, a PDI of 0.265, a critical micelle concentration (CMC) of 5.89 μg/mL, and a zeta potential of -15 mV. BSSA NPs showed good storage stability over 6 weeks. In a glutathione-rich environment, the drug release of BSSA NPs was more rapid than that of BCCA NPs. Concentration-dependent size analysis suggested that BSSA NPs were formed through a dynamic, reversible assembly process. Cellular uptake studies showed significantly increased internalization of BSSA NPs compared to free Ara-C, with enhancements of 4.13-fold in HeLa cells and 3.13-fold in A549 cells. Cytotoxicity assays demonstrated enhanced efficacy, reducing the IC50 by 67.9% in HeLa and 45.2% in A549 cells. The migration rate of HeLa cells was reduced to 14% after BSSA NPs treatment, in comparison with Ara-C treatment, and nuclear shrinkage and fragmentation were observed, indicating the potential of BSSA NPs to limit tumor progression and induce apoptosis. Importantly, no hemolysis was observed in BSSA NPs-treated groups, confirming their good biocompatibility. These findings suggest that BSSA NPs represent a promising strategy for targeted cancer therapy, combining enhanced drug delivery, antitumor efficacy, and biocompatibility.

Cardiac mitochondrial function is intricately regulated by various processes, ultimately impacting metabolic performance. Additionally, protein turnover is crucial for sustained metabolic homeostasis in cardiomyocytes.

Lung cancer is the leading cause of cancer deaths worldwide. Everolimus (Eve) was observed to upregulate the expression of phosphatase and tensin homolog and microRNA-4328 and inhibits the proliferation and migration of A549 cells. In the present study, a new nanocarrier based on composite containing chitosan (CS), carbon nanotubes (CNT) and ordered mesoporous (OMC) was used to load the anticancer drug everolimus (EVE). The existence of EVE on CNT/OMC/CS nanocarrier is confirmed by FE-SEM images, Raman, UV-Vis, FT-IR, BET and TGA analyses. The results showed that the introduction of CS improved the drug loading by 89.4% at pH 7.0, time 2 h and EVE to CNT/OMC/CS ratio of 1.5. Moreover, release study of EVE showed that 15.2% of EVE is released from EVE@CNT/OMC/CS at pH=7.4 for 15 h, while 78.9% of EVE is released at pH = 4.5. After 25 h, 16.8% and 88.0% of EVE were released at pH 7.4 and 4.5, respectively. Based on the MTT assay results, CNT/OMC/CS exhibited negligible cytotoxicity and good compatibility on the A549 lung cancer cell line. The cytotoxicity of the EVE@CNT/OMC/CS (IC50 of ~9 μg/mL) on the A549 cell line was higher as compared to free Eve drug (IC50 of ~13 μg/mL) after 48 h exposure time. All the data confirmed the synergistic effect of EVE in combination with CNT/OMC/CS could serve as an ideal candidate in treating lung cancer.

Caffeine (1, 3, 7-trimethylxanthine) can be used as an anti-cancer compound in low concentrations. Considering this potential and the advantages of nanotechnology, including targeted delivery and low doses of compounds, caffeine nanoparticles were produced using a spontaneous nanoemulsion production method. Nanoparticles with an average diameter of 168 ± 1.03 nm, a polydispersity index of 0.2, and desirable stability were produced. After treatment with free caffeine and caffeine nanoemulsion, the viability of K562 cancer cells was measured using the MTT test, which showed that free caffeine and caffeine nanoemulsion, after 48 h, killed 50% of cancer cells at a concentration of 555.23 ± 1.7 µg/ml and 285.71 ± 3 µg/ml, respectively. Evaluation of genes involved in the induction of apoptosis in cancer cells showed the prominent role of caspase-3 in the induction of apoptosis. Also, free caffeine and caffeine nanoemulsion increased the expression level of P53 by 2- and 4-fold compared to the control group, and the expression ratio of Bax/Bcl2 increased by 10- and 15-fold, respectively. The biocompatibility evaluation test results showed that the caffeine nanoemulsion in the concentrations used in this study had no cytotoxic effects on PMBC and RBC cells and could be used for therapeutic purposes. In general, the results of this study showed that caffeine nanoemulsions not only have more potent anti-cancer activity than free caffeine but also show minimal cytotoxicity and better biocompatibility than free caffeine on normal cells. Our findings show that caffeine nanoparticles are a potential candidate for cancer treatment use as a therapeutic agent.

The majority of patients with melanoma develop immune-related adverse events (irAEs), and over half do not respond to anti-PD-1 (Programmed cell death protein 1) checkpoint inhibitor (CPI) immunotherapy. Accurate predictive biomarkers for both response to therapy and development of irAEs are currently lacking in clinical practice. Here, we conduct deep immunophenotyping of circulating regulatory and class-switched B cell and antibody immune states in patients with advanced stage III/IV melanoma prior to and longitudinally during CPI.

Targeted therapy-induced acute kidney injury (AKI) can complicate oncologic treatment. We present a case of creatinine elevation induced by abemaciclib, a cyclin-dependent kinases 4 and 6 inhibitor used in advanced breast cancer which can also cause nephrotoxicity. A female patient in her mid-sixties was referred to nephrology for elevated serum creatinine after starting abemaciclib. Diagnostic workup, including blood urea nitrogen (BUN), serum cystatin C, urine protein measurement, and serum electrolytes revealed no evidence of renal dysfunction. This case emphasises the importance of distinguishing creatinine elevation from true nephrotoxicity to avoid unnecessary treatment adjustments. Abemaciclib and other targeted therapies can induce creatinine elevation by inhibiting proximal tubule secretory transporters, rather than through direct nephrotoxicity. By incorporating additional assessments such as BUN, serum cystatin C, and additional biomarkers including urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule 1, clinicians can distinguish creatinine elevation from AKI to guide appropriate management of oncologic diseases.

Stevioside and rebaudioside A revealed anticancer effects against diversity of cancers, such as colon, breast and liver cancers. Rebaudioside A can trigger apoptosis in cancer cells via activation of caspase-dependent pathway. In this study sodium alginate/poly(N-vinylpyrrolidone) as nano-carriers loaded with natural products rebaudioside A (R) and/or stevioside (S) were assessed for anticancer activities. The nanogel of structure R improved cytotoxicity against MCF-7, HepG2, HCT116 and A549 cancers by 60.29 %, 53.45 %, 72.86 % and 62.13 %, correspondingly. Additionally, the nanogel of structure S improved cytotoxicity against MCF-7, HepG2, HCT116 and A549 cancers by 63.96 %, 53.41 %, 70.59 % and 52.88 %, respectively. Furthermore, the nanogel for mixture of R/S improved cytotoxicity against MCF-7, HepG2, HCT116 and A549 cancers by 78.86 %, 54.75 %, 74.10 % and 56.53 % correspondingly. Also, cytotoxic activities of structures R, S and R/S and their nanogels exhibited low toxicity on VERO cells with IC50 = 30.90-46.50 μM and high selectivity against cancer cells. Moreover, R/S (nanogel), R (nanogel) and S (nanogel) demonstrated the uppermost binding affinities with DNA at reduced IC50 values of 31.50, 32.60, and 33.90 μM, respectively. In addition, they inhibited Topo-II activity with remarkably low IC50 value of 0.95, 1.00, and 1.10 μM, respectively.

To address the limitations of single therapy and ensure the safe and efficient delivery of nanomedicine, we developed carbon/manganese nanoparticles (NPs). These NPs were engineered by depositing manganese dioxide on the surface of mesoporous carbon (MMCN), thus enabling Peroxidase (POD)-Catalase (CAT)-Glutathione peroxidase (GPX)-like function. Following the modification with AS1411 aptamer (AMMCN), doxorubicin hydrochloride (DOX) was incorporated to produce AMMCN@DOX. This compound demonstrated satisfactory biocompatibility, efficient tumor tissue accumulation, and the capability to release DOX in response to the tumor microenvironment (TME). It was confirmed that AMMCN@DOX is effectively endocytosed by cells, releases DOX, decomposes H2O2 to generate O2 to alleviate tumor hypoxia, and mediates a Fenton-like reaction. Additionally, AMMCN@DOX showed excellent photothermal conversion efficiency, producing localized heating in tumors and yielding superior synergistic anti-tumor activity in mice with solid tumors. Thus, this study proposes a safe, targeted delivery strategy for carbon/manganese NPs, facilitating chemical, chemokinetic, and photothermal synergistic therapy.

This study investigated the 3-year development of chemotherapy-induced peripheral neuropathy (CIPN) in post-menopausal women diagnosed with early breast cancer (EBC) using vibration perception threshold (VPT) measurements and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (CIPN18). 90 patients (aged 50-70) and 30 healthy subjects were included in the study. VPT measurements and CIPN18 questionnaires were performed post-chemotherapy (median 72 (IQR: 53-93) days post chemotherapy) as well as at the 12 and 36-month follow-up. Post-chemotherapy data showed impaired VPT measurements when comparing our study population to controls, but spontaneous improvement occurred, and by the 36-month follow-up, VPT measurements normalized when compared to controls. Mean CIPN18 scores improved, though the improvement was not statistically significant. Spearman's rho between VPT measurements and CIPN18 questionnaires showed weak to moderate correlations during follow-up. However, further analyses using a Generalized Additive Model confirmed the absence of a significant correlation between VPT measurements and CIPN18 questionnaires. Our data highlight limitations in the relationship between VPT measurements and CIPN. However, VPT measurements may have potential as an objective supplement to general assessment of patients.

Current first-line treatment for patients with metastatic melanoma with BRAFV600E or BRAFV600K mutations includes immunotherapy with immune checkpoint inhibitors and targeted therapy; however, the optimal sequencing of these treatments is unclear. We aimed to investigate the use of a targeted-therapy induction regimen before treatment with immune checkpoint inhibitors.

Acute promyelocytic leukemia (APL) is highly malignant and progresses rapidly. In recent years, several studies have shown that oral arsenic, the primary component is realgar, could effectively alleviate APL, with therapeutic effects not inferior to those of intravenous arsenic and a higher safety profile, but currently the active substances and mechanism of realgar's anti-APL effect are unclear, making oral arsenic agents containing realgar lack sufficient scientific basis clinically. The clinical trials on oral arsenic agents containing realgar for the treatment of APL over the past 20 years were reviewed, suggesting it had good therapeutic effect and relatively high safety. Quantitative analysis was conducted on the accumulation of arsenic metabolites in different tissues during the longest 90 day period after realgar administration in rats, and it was found that dimethylarsenic (DMA) was the most predominant form of arsenic metabolites in the body. The DMA concentration slightly increased and remained stable with prolonged administration time, even if discontinuation, the DMA concentration still remained at a certain level. Distribution and accumulation of DMA were significantly higher in blood than in organs. Futhermore, DMA significantly prolonged the survival time of APL mice, induced cell apoptosis, inhibited NB4 cell proliferation, promoted the differentiation of leukemia cells, and downregulated the expression of PML-RARα fusion protein and wild-type RARα protein. The study concluded that DMA could be the main active substance of realgar and is responsible for its significant anti-APL effects, suggesting realgar has good efficacy for blood-related diseases and have low hepatorenal toxicity.

Histone deacetylases (HDACs) have been explored as anticancer targets for over two decades, with six HDAC inhibitors approved for clinical use. However, these pan-HDAC inhibitors exhibit off-target effects, necessitating the development of isoform-selective inhibitors. Among HDACs, HDAC6 has garnered attention due to its dual catalytic domains, cytoplasmic localization, and zinc-finger ubiquitin-binding domain (Zf-UBD). Its role in gene expression, proliferation, protein homeostasis, and cell cycle regulation make it an attractive anticancer target. Here, we report on the design and synthesis of indazole-based HDAC6 inhibitors and evaluate the impact of zinc-binding group (ZBG) modifications on pharmacokinetics. Compound 5j emerged as a selective and potent HDAC6 inhibitor (IC50 = 1.8 ± 0.3 nM), exhibiting strong antiproliferative activity against HCT116 cells (GI50 = 3.1 ± 0.6 μM). It preferentially induced α-tubulin acetylation over histone H3 at concentrations as low as 0.5 μM which is a hallmark of HDAC6 selective inhibition. However, its hydroxamic acid-based ZBG resulted in a very low oral bioavailability (1.2 %). To address this limitation, compound 12 was synthesized with an ethyl hydrazide ZBG, significantly improving oral bioavailability (53 %). These findings highlight compound 12 as a promising lead for further pharmacophore optimization, paving the way for clinically viable HDAC6 selective inhibitors with enhanced drug-like properties.

Proteolysis-targeting chimera (PROTAC) technology was employed to achieve the degradation of PI3Kδ in this study, and a series of PROTAC-based PI3Kδ degraders were first developed. Lysine-targeted covalent strategy led to the discovery of novel potent PROTAC-based PI3Kδ degraders. After screening and structure-activity relationship study, B14 was optimal and exhibited strong antiproliferation and selective PI3Kδ inhibition, with a high degradation value (DC50 = 3.98 nM). B14 induced cell cycle arrest in the premitotic phase and prompted cell apoptosis. B14 displayed effective suppression of the tumor growth in the xenograft model and significantly promoted the PI3Kδ degradation in vivo. Most importantly, B14 bound to the Lys779 of PI3Kδ to selectively degrade PI3Kδ by covalent-bonding. Mechanistic studies indicated that the ubiquitin-proteasome pathway was involved in the degradation process. This study provided an effective approach for developing PROTAC-based PI3Kδ degraders, and the lysine-targeted covalent strategy laid the foundation for the further design of potent PI3Kδ-targeting PROTACs.

Blocking NAD+ biosynthesis presents an appealing strategy for antitumor therapies. This study developed a series of o-aminobenzamide derivatives with substantial antitumor efficacy against gastric cancer. Notably, compound 9a demonstrated exceptional antitumor activity against undifferentiated gastric cancer HGC27 cells (IC50 = 0.049 μM), and significant inhibitory effects on cellular proliferation, self-renewal, invasion, and migration. Mechanistic investigations revealed that 9a could damage mitochondria, arrest the cell cycle, promote apoptosis, and alter cellular metabolism. Furthermore, the rate-limiting enzyme NAMPT in the NAD+ salvage synthetic pathway was identified as a primary target of 9a. By inhibiting NAMPT, 9a reduced intracellular levels of NAD+ and ATP, while NMN, a natural product of NAMPT, counteracts its antimetabolic and cytotoxic effects. Overall, this study highlights 9a as a promising NAMPT inhibitor with significant activity against undifferentiated gastric cancer, laying the groundwork for developing novel antigastric cancer agents through inhibiting NAD+ biosynthesis.

The KRAS (Kirsten rat sarcoma viral oncogene homolog) gene is recognized as the most frequently mutated oncogene in advanced non-small cell lung cancer (NSCLC). The most prevalent mutation within this gene is G12C, formally known as KRAS G12C, which leads to the substitution of glycine with cysteine at position 12 of the KRAS protein.

Despite their unique advantages and vast potential, nanomaterials employed in cancer therapy still encounter challenges such as uneven biodistribution, unintended drug leakage, and especially potential tissue damage caused by off-target toxicity. Bioinert nanomaterials, known for their excellent chemical stability, and minimal biological reactivity, can exert localized tumoricidal effects in response to specific external stimuli. However, the lack of precise control or poor penetration depth largely limits the therapeutic efficacy, necessitating the development of innovative stimuli-responsive therapeutic strategies. This study presents an alternative drug-responsive cancer therapeutic approach based on nickel-iron layered double hydroxide (NiFe-LDH), which exhibited negligible toxicity to both normal cells and cancer cells. By conjugating a platelet-derived growth factor receptor (PDGFR)-β-targeting cyclic peptide, NiFe-LDH achieved high specificity for prostate cancer cells, significantly enhancing tumor targeting and accumulation. Upon administration of deferoxamine mesylate (DFOM), an FDA-approved iron chelator, NiFe-LDH transitioned from a "bioinert" state to a "bioactive" nanotherapeutic through structural disassembly and robust release of nickel ions (Ni²⁺). The released ions disrupted mitochondrial function, upregulated insulin-like growth factor binding protein 3 (IGFBP3), and further inhibited the PI3K/AKT/mTOR signaling pathway, consequently leading to potent and selective induction of apoptosis in prostate cancer cells. Unlike conventional therapies, which often cause varying degrees of toxicity in non-target organs, this stimuli-responsive nanoplatform could minimize off-target effects and systemic toxicity by combining the non-toxic LDH with the clinically used DFOM. Our findings demonstrate that DFOM-responsive NiFe-LDH can effectively inhibit tumor growth in both cultured cells and tumor xenografts, suggesting a rational and clinically translatable platform for precision cancer therapy.

This study aimed to compare changes in postural control in different testing conditions involving sensory disturbances, quality of life and neurotoxicity concerns in women with cancer before and after chemotherapy with taxanes. The second aim was to compare postural control between chemotherapy-induced peripheral neuropathy (CIPN) severity subgroups.

Patients with cancer during antineoplastic infusion therapy live an existential period characterized by experiences of profound psychological, physical, social, and spiritual changes.

Paclitaxel Injection Concentrate for Injection (PICN) is a novel nanoparticle formulation designed to overcome the limitations associated with the administration of marketed Cremophor and albumin based (nab) paclitaxel formulations. This study compared the in vivo antitumor efficacy of PICN with that of solvent-based paclitaxel and nab-paclitaxel in a murine NMRI nu/nu athymic nude mouse model bearing various human tumor xenotransplants: head and neck cancer (HNXF 1838 and HNXF 1842), lung cancer xenografts (LXFA 1584), and breast cancer xenografts (MAXF 574 and MAXF 1384). PICN displayed good to excellent antitumor activity. Moreover, PICN inhibited tumor growth more than solvent based paclitaxel formulation when compared at comparable tolerated dose levels. The higher antitumor efficacy of PICN compared to paclitaxel at lower dose levels of half the maximum tolerated dose (1/2MTD) was significant (P < 0.05) in three of the tumor models, i.e. HNXF 1842, MAXF 574, and MAXF 1384. The higher efficacy of PICN compared to paclitaxel was also evident at the MTD, but somewhat less pronounced, and was significant (P < 0.05) in one tumor model (HNXF 1838). The antitumor activity of PICN was similar to that of nab-paclitaxel. However, in one tumor model (HNXF 1838) PICN 50 mg/kg (1/2 MTD) showed a slight benefit over the same dose of nab-paclitaxel. The nanoparticulate nature of PICN and nab-paclitaxel therefore seems to enhance tumor cell penetration compared to conventional paclitaxel, resulting in better antitumor efficacy.

Psoralea bituminosa L. (Fabaceae) is a medicinal plant traditionally used for its antimicrobial, antihyperglycemic, and antioxidant effects. This study investigated its anticancer and antioxidant potential using aqueous and methanol extracts. The methanol extract exhibited higher total phenol (81.57 mg/g) and total flavonoid (39.06 mg/g) contents compared to the aqueous extract. Antioxidant activity, assessed via the DPPH assay, showed moderate potency (IC₅₀: 330.77 µg/mL for aqueous- and 348.27 µg/mL for methanol extracts). Notably, the methanol extract demonstrated significant cytotoxicity against multiple cancer cell lines (IC₅₀: 27.73-53.90 µg/mL) particularly against A549, MDA-MB231, and PC3. Liquid chromatography-mass spectrometry (LC-MS) profiling revealed abundant flavonoids and isoflavones such as daidzein, biochanin A, and 7,3'-dimethoxy-5,6,4' trihydroxyisoflavone in the methanol extract, correlating with its anticancer effects. In contrast, glycosylated flavonoids in the aqueous extract aligned with antioxidant activity. Cheminformatics clustering supported these findings, identifying distinct structural groups with differing drug-likeness scores. Bioinformatics analysis further identified transcriptomic signatures enriched in oxidative phosphorylation and key cancer-related pathways (e.g., TP53, PI3K, NRF2, and MYC), offering mechanistic insight. This integrative approach combining LC-MS, cheminformatics, and bioinformatics provides a cost-effective framework for decoding phytochemical bioactivity and guiding natural product-based drug discovery.