Zwitterionic polymers have emerged as a powerful platform for constructing stealth nanocarriers owing to their superior antifouling capability and excellent biocompatibility. Herein, we report a biodegradable zwitterionic nanogel, P(VCL-ss-OrnAA), featuring synergistic thermo-and redox-responsiveness, prepared via aqueous precipitation copolymerization of N-vinylcaprolactam (VCL), ornithine methacrylamide (OrnAA), and a disulfide-containing crosslinker. The incorporation of ornithine-derived zwitterionic moieties endows the nanogels with remarkable colloidal stability and pronounced resistance to nonspecific protein adsorption, conferring desirable stealth characteristics in biological environments. The nanogels exhibit a well-defined temperature-triggered swelling-to-collapse transition in aqueous media, together with efficient redox-responsive degradation mediated by disulfide linkages under reductive intracellular conditions. When loaded with doxorubicin (DOX), the nanogels display negligible premature leakage under physiological conditions, accelerated drug release at elevated temperatures, and rapid payload liberation in reductive environments, enabling spatiotemporally controlled drug delivery. In vitro studies demonstrate minimal cytotoxicity of blank nanogels toward both normal and cancer cells, while DOX-loaded P(VCL-ss-OrnAA) nanogels achieve significantly enhanced tumor cell growth inhibition compared with DOX-loaded PVCL counterparts. Furthermore, in a colorectal tumor-bearing mouse model, the nanogel formulation exhibits pronounced tumor suppression efficacy. Collectively, these results highlight P(VCL-ss-OrnAA) nanogels as a promising zwitterionic nanoplatform for precision cancer therapy.

Recently, hydrogen sulfide (H2S) has been recognised as a promising member of the gasotransmitter family, which plays a vital role in regulating various physiological and pathological processes. Hence, the development of synthetic chemical tools capable of donating H2S in a controlled manner is an area of substantial interest. Herein, we developed a two-photon-activated photoresponsive COS/H2S donor that exploits the long-range excited-state intramolecular proton transfer (ESIPT) phenomenon in our designed system. This platform uses a photocage tethered to a thiocarbamate moiety, which, upon light irradiation, releases COS. The released COS could be rapidly hydrolysed by carbonic anhydrase and generate H2S, closely mimicking the body's well-regulated endogenous H2S production. Additionally, the incorporation of the long-range ESIPT process offers several advantages, such as (i) strong emission with a large Stokes shift and (ii) a faster photorelease rate. TD-DFT calculations carried out using the CAM-B3LYP density functional with the TZVP basis set further validated our experimental findings. Intrigued by these properties, we also developed our photoresponsive COS/H2S donor HQ-COS as a nanoprodrug (nano-HQCOS) and explored its therapeutic potential in the MDA-MB-231 triple-negative breast cancer cell line. In vitro studies demonstrated that our nano-HQCOS exhibits effective cellular internalisation and inhibits the growth of triple-negative breast cancer cells, particularly those with overexpressed carbonic anhydrase, while it is benign to the normal healthy cells.

Despite being considered a gold standard chemotherapeutic drug, cisplatin is associated with dose-limiting toxicity, especially nephrotoxicity. This highlights the need for safe and effective adjuvant agents that protect against cisplatin-induced toxicity without affecting its anticancer activity. This study investigated the potential of Momordica balsamina aqueous extract (MBAE) as an adjuvant to reduce cisplatin-induced kidney cell damage and death.

Although strategic combination of cuproptosis and chemotherapy is emerging as a promising strategy against triple-negative breast cancer (TNBC), current drug delivery systems remain considerable challenges in achieving co-delivery of different formulas, such as complex nanocarrier design, limited drug loading capacity, and insufficient tumor targeting. Herein, cancer cell membrane-camouflaged, self-assembled nanoparticles (DCM@CCM) were fabricated for precision combination therapy against TNBC. In the strategy, the carrier-free self-assembled nanoparticles were one-pot fabricated by co-assembling copper ions (Cu2+), doxorubicin (DOX), and methotrexate (MTX) via hydrogen bonds, π-π stacking and metal-ligand coordination effect, followed by in situ camouflaging with cancer cell membranes. Benefiting from the homologous targeting effect, the developed DCM@CCM could specifically target tumor cells, promoting their cellular uptake. Following internalization into tumor cells, the DCM@CCM disassembled in response to a weakly acidic tumor microenvironment, releasing Cu2+, DOX, and MTX. Importantly, the Cu2+ was reduced to Cu+ by depleting intracellular glutathione, which not only activated cuproptosis but also catalyzed the endogenous hydrogen peroxide into highly toxic hydroxyl radicals via a Fenton-like reaction, resulting in mitochondrial dysfunction. Simultaneously, both DOX and MTX disrupted DNA synthesis to trigger cell apoptosis. Both in vitro and in vivo experiments indicated that DCM@CCM exhibited potent cytotoxicity against TNBC cells and effectively suppressed tumor growth in heterotopic tumor models with minimal side effects. Overall, our study not only provides a promising strategy for precision combination therapy against TNBC but also expands insight for developing nanoscale self-assembly-enabled nanomedicine.

Lung cancer presents complex etiopathology involving a mix of genetic predispositions and environmental factors. The best treatment modality is surgical resection. However, it becomes ineffective in the advanced metastatic stage. Thus, cisplatin-based chemotherapy, though restricted by an intrinsic and/or acquired chemo-resistant phenotype, remains the first-line therapy for advanced non-small-cell cancer (NSCLC).

Eliminating both senescent and cancer cells through pharmacological intervention presents a powerful therapeutic strategy against aging and tumor progression. Navitoclax has emerged as a promising candidate with both senolytic and antitumor activity, but its clinical application remains limited due to dose-dependent thrombocytopenia and tumor-specific resistance. To overcome these limitations, we combined dichloroacetate and metformin with a 10-fold reduced dose of Navitoclax (ABT-263) and show that this pharmacology, termed, DMA, selectively targets the metabolic vulnerabilities underlying senescent and malignant cells. We demonstrate that DMA effectively ablates different types of senescent and cancer cells in vitro by exacerbating their defects in ATP production. Notably, the treatment is well tolerated by healthy human cells and in mice in vivo, and in fact improves the functional performance of aged mice after acute administration and extends lifespan after prolonged dosing. While the in vivo effects of DMA are yet to be fully explored, our findings suggest that it might represent a new, clinically viable way to combat cancer and senescence without toxicity to healthy cells and tissues.

Ultrasound-induced luminescence offers a light-free imaging modality with deep tissue penetration and spatiotemporal controllability; however, its broader application is hindered by weak luminescent signals that limit imaging depth and signal-to-noise ratios. Here, we report an organic-inorganic heterojunction sonosensitizer, TA@TiO2, formed by coupling a trianthracene derivative (TA) with titanium oxide (TiO2). Under ultrasound irradiation, the nanoscale charge-transfer interface promotes interfacial charge transfer, significantly enhancing reactive oxygen species (ROS) generation. This increased ROS triggers amplified chemical energy conversion, resulting in a markedly enhanced ultrasound-induced luminescence signal for deep-tissue optical imaging. Compared to TA nanoparticles, TA@TiO2 exhibits superior signal transmission in scattering media and maintains high luminescence at lower power densities. In vivo studies demonstrate that TA@TiO2 enables high-contrast imaging of deep-seated tumors, such as pancreatic cancer and glioma, while providing enhanced sonodynamic therapy efficacy. The positive correlation between ultrasound-induced luminescence intensity and ROS generation allows for dynamic, imaging-guided tumor therapy. These results establish heterojunction engineering as a potent strategy for advancing ultrasound-activated theranostics.

Trichodermin, a sesquiterpene antibiotic from Trichoderma species, shows anticancer potential. In this study, anti-glioblastoma activity was evaluated by (3-(4,5-di methyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay, colony formation, lactate dehydrogenase (LDH) release assay, flow cytometry, wound-healing, transwell invasion, adhesion, Western blot, combination-index analysis, and an orthotopic luciferase glioblastoma mouse model. Trichodermin reduced viability and clonogenicity and increased LDH release of T98G and A172 cells. Trichodermin induced G2/M arrest with p53 activation and downregulation of cyclin B, cyclin A, and cyclin-dependent kinase 1 (CDK1). In addition, trichodermin induced caspase-dependent apoptosis. Invasion, wound healing, and adhesion were suppressed with modulation of epithelial-mesenchymal transition (EMT)-related proteins. Combination index analysis demonstrated a synergistic interaction between trichodermin and temozolomide, possibly due to increased apoptosis. In the mouse model, intraperitoneal trichodermin inhibited intracranial tumour growth and prolonged survival, and increased cleaved caspase-3 expression in tumour tissues. These findings indicate that trichodermin exerts anti-glioblastoma activity and warrants further preclinical evaluation as a potential adjunct to temozolomide therapy.

Chemotherapy-induced neutropenia (CIN) is a common dose-limiting toxicity in patients with solid tumors, often leading to infections, treatment delays, or dose reductions. However, studies on the dynamic patterns of CIN across multiple chemotherapy cycles and their prediction remain limited.

Colorectal cancer (CRC) is a prevalent gastrointestinal carcinoma. Huanglian decoction (HD) has been applied to treat gastrointestinal disorders for millennia.

Hand-foot skin reaction (HFSR) is a dose-limiting adverse effect of sorafenib, yet its molecular etiology remains elusive.

In this work, we prepared a series of substituted imidazole-derived Ru(III) complexes, ImRu1-ImRu5, analogous to the clinically evaluated NAMI-A. These Ru(III) complexes, with different functional groups on the imidazole ring, were characterised by 1H NMR and UV-Vis spectroscopy, elemental analysis, low- and high-resolution mass spectrometry, and single crystal X-ray diffraction. The cytotoxicity of the Ru(III) complexes was evaluated in vitro against different cancer and non-cancer cell lines, exhibiting low cytotoxicity activity and antimigratory characteristics comparable to those of the NAMI-A complex, except for the Ru(III) complex bearing an alkyne substituent on the imidazole ring (ImRu3). ImRu3 exhibited selective cytotoxicity against A549, MeWo and T24 cells, while retaining antimigratory activity against T24 cells, indicating that modifications at the imidazole ligand can modulate biological behaviour. Computational and fluorescence studies suggest that functional variations of the imidazole ligand enhance albumin-binding affinity, potentially facilitating transport and contributing to the observed anticancer activity.

Nanoparticle-based drugs face challenges of weak spatiotemporal control and difficulty in elucidating their mechanisms of action. We designed a stimulus-responsive delivery system based on targeted peptides and quantum dots (QDs) to achieve synergistic therapy combining sonodynamic therapy (SDT) and immune checkpoint blockade (ICB). Using spatially resolved proteomics technology, we analyzed the mechanism underlying this synergy.

Tenosynovial giant cell tumors (TGCT) are rare, locally aggressive neoplasms causing pain, stiffness, swelling, limited range of motion, and joint degeneration, which can be debilitating. Therapeutic options include surgery or systemic therapy with colony-stimulating factor 1 receptor (CSF-1R) pathway inhibitors. However, many are not amenable to surgery or have high postsurgical recurrence rates. Available systemic therapies require long-term administration and can have burdensome side effects. Emactuzumab is a novel, potent, CSF-1R inhibiting monoclonal antibody with a unique mechanism of action targeting the receptor dimerization interface of the CSF-1R to reduce tumor-associated macrophages and inflammation within the TGCT microenvironment. It is the only short-course, intravenous therapy in development for TGCT. In a phase I study, emactuzumab resulted in robust and durable responses, and a manageable safety profile in patients with TGCT, supporting further research as a treatment option to address unmet need and improve quality of life in patients with TGCT. TANGENT is a randomized, double-blind, global, phase III study (NCT05417789) to investigate the safety and efficacy of intravenous emactuzumab versus placebo in patients with TGCT not amenable to surgery.Clinical trial registration: www.clinicaltrials.gov identifier is NCT05417789 initially registered on 1 June 2022.

Vincristine is a cornerstone of pediatric chemotherapy, but its use is limited by vincristine-induced peripheral neuropathy (VIPN). Paradoxically, African children tolerate higher vincristine doses with minimal neurotoxicity, raising questions about the pharmacological mechanisms and model generalizability across populations. In this study, we re-estimated vincristine pharmacokinetic (PK) and PK-pharmacodynamic (PKPD) models using data from both Dutch and Kenyan pediatric cohorts and designed five simulation scenarios to assess the impact of Type I (informative censoring) and Type II (population-specific effect modifier) selection bias on model predictions. A three-compartment PK model with saturable distribution and a proportional-odds PKPD model with Markov elements jointly described vincristine disposition and VIPN risk. Kenyan children showed lower clearance but markedly reduced PD sensitivity, resulting in negligible predicted VIPN even at higher doses. Incorporating informative censoring improved internal validity by capturing the observed dropout dynamics, while mechanistic extrapolation using CYP3A5, ABCB1, and CEP72 genotype distributions increased external validity and aligned model predictions better with empirical outcomes. Clinically, these findings support population-specific vincristine dosing strategies and suggest that reduced neurotoxicity in African children reflects lower neuronal susceptibility rather than reduced systemic (plasma) exposure. Methodologically, this work demonstrates how unrecognized selection bias can distort PKPD extrapolations across populations and highlights the value of integrating mechanistic and genetic information within model-based frameworks to improve the safety and external validity of model-informed dosing strategies beyond the original study populations.

In the era of precision medicine, targeting resistance mechanisms is a rational approach to optimize treatment management based on tumor molecular profiling, with the goal of improving clinical outcomes. However, the role of tailored strategies in the treatment algorithm of EGFR-mutated NSCLC remains incompletely defined.

Bicaudal-C homolog 1 (BICC1) is an essential RNA-binding protein that plays a significant role in cellular signaling and gene expression regulation. Recent research has linked the BICC1 gene to the initiation and advancement of tumors. Current investigations primarily aim to elucidate its structural characteristics and functional roles, while its precise involvement in tumorigenesis and its viability as a therapeutic target are still being explored. This review delves into the structure and functions of BICC1, emphasizing its participation in tumor cell growth, programmed cell death, epithelial-mesenchymal transition (EMT), blood vessel formation, maintenance of stem cells, and chemoresistance. Furthermore, it examines progress in developing drugs that target BICC1 for cancer therapy and evaluates the potential advantages of traditional Chinese medicine in mediating anti-tumor effects through BICC1 modulation, offering perspectives for future targeted treatment strategies.

Despite the clinical success of immune checkpoint inhibitors (ICIs), resistance driven by a metabolically hostile tumor microenvironment (TME), particularly lipid metabolic reprogramming, remains a formidable challenge. Tumors actively exploit lipid mediators, notably prostaglandin E2 (PGE2), to suppress CD8+ T cells and promote immunosuppressive macrophage polarization. Although targeted nanotherapeutics aim to locally reverse these defects, their in vivo efficacy is frequently abrogated by the host's nutritional baseline. Specifically, high dietary intake of Omega-6 polyunsaturated fatty acids fuels systemic PGE2 biosynthesis, creating a metabolic "sink" that localized nanotherapies struggle to neutralize. To address this limitation, this review proposes a dual-compartment therapeutic framework combining systemic dietary modulation with precision nanotherapy. As a distinctive contribution, we bridge these biological mechanisms with pharmaceutical design by integrating critical translational barriers, advanced formulation strategies, and emerging technologies for lipid reprogramming. Building upon this, we critically evaluate the most promising formulations, including stimuli-responsive and lipid-targeted nanocarriers, to elucidate their synergistic potential with nutritional interventions. Ultimately, pairing systemic Omega-3 dietary preconditioning with localized nanotherapeutics provides a biologically rational strategy to dismantle lipid-driven immune evasion. Maximizing patient outcomes and advancing future clinical prospects will depend on the rigorous translation of these combinatorial regimens to effectively overcome ICI resistance.

This study focused on biological activities and chemical characterization of secondary metabolites from the fungus Talaromyces annesophieae MD2 (GenBank: PQ252671). The dichloromethane extract (DCM-E) of its culture supernatant was fractionated using chromatographic techniques. Initially, three main fractions were first prepared from DCM-E. Subsequently, the selected active fraction 2 was subfractionated into six subfractions. The subfraction 3 demonstrated high water solubility and strong antibacterial activity against both gram-positive and gram-negative bacteria (MIC values of 105.41, 82.76, 71.92, and 70.38 µg/mL against B. cereus, S. aureus, E. coli, and K. pneumoniae, respectively). It exhibited selective anticancer activity through regulation of autophagy- and apoptosis-related pathways without affecting healthy cells (IC50 values of 7.65, 3.76, 10.76 µg/mL against HT-29, DU-145 and SH-SY5Y, respectively). Furthermore, it exhibited DPPH and ABTS radical-scavenging activities (48.3% and 44.1% at the concentration of 100 μg/mL, respectively) and protected dermal fibroblasts against H2O2-induced toxicity. Structural analyses elucidated that the subfraction 3 contained four nitrogenous polar compounds. Three compounds (C5H3O4N8, C15H25O4N4, and C23H21N4) were suggested to be alkaloid-like or nitrogen-rich heterocyclic secondary metabolites, while the remaining compound (C9H9O4N) was probably an aminobenzoic acid-type or heteroaromatic carboxylic acid derivative. This is the first report on bioactive metabolites of T. annesophieae. Due to multifunctional biological activities, its metabolites can find application in dermocosmetics and pharmacology.

The genus Kalanchoe Adans. is recognized for its medicinal importance and broad pharmacological profile, notably its antitumor activity, often attributed to flavonoids and bufadienolides. This study aimed to establish a comparative chemical profile and investigate the inhibitory potential against B16F10 melanoma cells of aqueous extracts from aerial parts and roots of seven Kalanchoe species - K. delagoensis (KD), K. fedtschenkoi (KF), K. gastonis-bonnieri (KGB), K. × houghtonii (KH), K. laetivirens (KL), K. pinnata (KP), and K. thyrsiflora (KTY) - focusing on the biochemometrics-based identification of bioactive substances. The extracts were cleaned up by RP-18 SPE and characterized by HPLC-DAD and HPLC-MS/MS. Beyond flavonoid glycosides and bufadienolides, this study mapped a diverse array of flavan-3-ols, proanthocyanidins, and gallic acid derivatives in aerial parts and roots. This is the first report of KF, KGB, KH, KL, and KD roots potent toxicity to B16F10 cells. Among aerial parts, only KD showed comparable efficacy. Statistical correlations suggested that gallic acid and galloyl-bound derivatives are the primary contributors to anti-melanoma activity. This was corroborated by the isolation of five bioactive compounds from KD aerial parts: two galloylglucosides-gallic acid 4-O-(6'-O-galloyl)-glucopyranoside (1 - GAGG; IC50: 84.2 μM) and 1,6-di-O-galloylglucopyranose (2 - DGG; IC50: 95.6 μM)-alongside three galloylated flavan-3-ols - epigallocatechin gallate (3 - EGCG; IC50: 26.8 μM), 3'-O-methyl epigallocatechin gallate (4 - MEGCG; IC50: 17.0 μM), and 3',5'-O-dimethylepigallocatechin gallate (5 - DMEGCG; IC50: 12.8 μM). This study provides new insights into the phytochemical profile and bioactivity of Kalanchoe species, with a special emphasis on roots, a plant part understudied.