DRUG METABOLISM AND DISPOSITION
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2026
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IF 3.6
Jiayi Yao,Jiaqi Wang,Peipei Bu,Kexin Liu,Mingyang Zhao,Jingkai Gu,Xiangjun Meng
Fluorescent probes are extensively used for tracking the in vivo behavior of nanocarriers. However, the impact of fluorescent probes on the in vivo fate of nanomedicines remains uncertain. Potential interference from the probes may lead to misleading conclusions. This study investigated the influence of a commonly used fluorescent probe, DiI, on the in vivo fate of paclitaxel (PTX)-loaded polymeric micelles (PMs) in rats. The drug release kinetics of PTX-loaded PMs (PTX-PM) with DiI/PTX co-loaded PMs (DiI/PTX-PM) in rat plasma was quantitatively compared. The results indicate that co-encapsulation with DiI significantly exacerbated drug release and altered the protein binding of PTX through competitive binding, resulting in an increased proportion of free PTX. DiI enhanced diffusion-driven drug leakage without affecting the micelle dissociation kinetics. Notably, DiI inhibited elimination and increased the systemic exposure of both the free micelle material and the nanocarrier. This study provides evidence that DiI can potentially interfere with the in vivo fate of both the therapeutic payload and the nanocarrier, highlighting the necessity for rigorous validation when employing it for nanocarrier tracking.
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PHYTOMEDICINE
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2026
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IF 11.3
Huihui Shi,Feifei Li,Meng Wang,Mengyue Zhu,Bei Deng,Dongpo Li,Yuming Yao,Meiling Zhou
The FA-modified pH-sensitive micelles (FA-PM@QCT/PTX) can enhance tumor targeting and lysosome-triggered drug release. • The system reverses chemotherapy resistance via the synergistic action of co‑delivered quercetin and paclitaxel, significantly enhancing cytotoxicity and inducing apoptosis in drug‑resistant cancer cells. • The system demonstrates potent antitumor efficacy with excellent biocompatibility in vivo , markedly inhibiting tumor growth while showing minimal systemic toxicity. Background Chemotherapy remains a major challenge in the effective treatment of non-small cell lung cancer (NSCLC), particularly due to chemotherapy resistance. Natural products, including Chinese herbal extracts, have shown potential for improving chemotherapy sensitivity, but their clinical application is limited by poor tumor targeting and insufficient in vivo stability. Purpose This study aimed to improve PTX-based treatment against resistant NSCLC by developing a FA receptor-targeted pH-sensitive co-delivery system for QCT and PTX. Study design A novel FA receptor-targeted pH-responsive nano-delivery system, FA-PM@QCT/PTX, was constructed and evaluated using PTX-resistant A549/Taxol cells and A549/Taxol tumor-bearing mouse models. Methods FA-PM@QCT/PTX was prepared and characterized in terms of particle size, PDI, zeta potential, encapsulation efficiency, and drug-loading content. In vitro pH-responsive release, cellular uptake, QCT/PTX synergism, cytotoxicity, apoptosis, cell-cycle distribution, P-gp expression, PI3K/Akt signaling, apoptosis-related proteins, and intracellular PTX retention were evaluated in A549/Taxol cells. Pharmacokinetics, tissue distribution, antitumor efficacy, survival benefit, and preliminary systemic safety were further assessed in A549/Taxol tumor-bearing mice. Results FA-PM@QCT/PTX showed a particle size of 166.75 ± 4.10 nm, a PDI of 0.14 ± 0.03, and a zeta potential of -6.34 ± 0.52 mV. The encapsulation efficiencies were 82.48 ± 3.82% for QCT and 84.17 ± 1.21% for PTX, with drug-loading contents of 3.64 ± 0.17% and 3.59 ± 0.11%, respectively. The self-assembled micelles could be internalized by tumor cells via FA receptor-mediated uptake and promote drug release under acidic lysosomal conditions. Chou-Talalay analysis showed that QCT enhanced the inhibitory effect of PTX on A549/Taxol cells, and the actual PTX:QCT molar ratio in FA-PM@QCT/PTX was approximately 1:3, which remained synergistic with a combination index (CI) value of 0.927 ± 0.021. Mechanistically, FA-PM@QCT/PTX reduced P-gp expression, enhanced intracellular PTX retention, suppressed PI3K/Akt signaling, and promoted apoptosis-related pathway activation. In vivo , FA-PM@QCT/PTX improved tumor drug accumulation and prolonged the median survival of A549/Taxol tumor-bearing mice to 52 days without obvious systemic toxicity. Conclusions These results suggest that FA-PM@QCT/PTX may provide a promising co-delivery strategy for improving PTX-based treatment against resistant NSCLC. Download: Download high-res image (371KB) Download: Download full-size image
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2026
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IF 5.7
Tong Zhao,Luying Xu,Wenjie Huang,Cong Wang,Huanhuan Wang,Mengyue Du,Chang Yao,Yanlei Xu
Background Breast cancer progression depends on abnormal angiogenesis, driven by VEGF/VEGFR2/ERK and inhibited by Angiotensin-Converting Enzyme 2 (ACE2). Chrysophanol (CHR) shows anti-breast cancer efficacy, but its mechanism is unclear. Methods Anti-tumor effects were assessed by measuring tumor volume, H&E staining, Ki67 immunohistochemistry, MTT, scratch wound, and Transwell assays. Anti-angiogenic effects were evaluated via Platelet Endothelial Cell Adhesion Molecule-1 (CD31) immunohistochemistry, CAM assay and Western blot (WB) of VEGF-A, Hypoxia-Inducible Factor 1-α (HIF-1α), and VEGFA/VEGFR2/ERK pathway proteins. The mechanism was explored by WB analysis of ACE2 expression/ubiquitination, validated by siRNA knockdown and CETSA for binding site identification. Results Both in vivo and in vitro experiments demonstrated that chrysophanol reduces tumor cell viability, suppresses tumor cell growth, migration, and invasion, inhibiting the progression of breast cancer. Given the critical role of angiogenesis in tumor development, further studies revealed that chrysophanol downregulates the expression of proteins such as HIF-1α and Vascular Endothelial Growth Factor A (VEGFA), indicating that it inhibits tumor angiogenesis by suppressing the VEGFA/VEGFR2/ERK signaling pathway. Since prior evidence suggests that this pathway acts downstream of ACE2, we examined ACE2 protein levels and found that chrysophanol reduces ACE2 ubiquitination, and enhances its stability and expression. This upregulation of ACE2 further inhibits the downstream VEGFA/VEGFR2/ERK pathway. Moreover, molecular docking confirmed that chrysophanol binds specifically to the active pocket 888 of the ACE2 protein. All the observed inhibitory effects on breast cancer were dose-dependent. Conclusion All the data shows that chrysophanol can reduce tumor angiogenesis and alleviate breast cancer growth. It also confirms that chrysophanol can promote ACE2 expression to inhibit the VEGFa/VEGFR2/ERK signaling pathway, thereby suppressing breast cancer development.
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
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IF 5.9
Ying He,Nengbin Wan,Hongwu Deng,Yi Zhang,Qiang Liu,Li Li,Hao Liu,Xiao He,Qing Zhu
Triple-negative breast cancer (TNBC) is an aggressive malignancy often characterized by chemoresistance, partly due to the overexpression of drug efflux transporters like ABCG2. To address this challenge, this study developed and evaluated a cRGD-modified, pH-sensitive liposomal system for the targeted co-delivery of docetaxel (DTX) and siRNA against ABCG2 (si-ABCG2). The synthesized nanoparticles (DTX/siRNA/cRGD-PLPs) exhibited optimal physicochemical properties, including a mean particle size of approximately 241.7 nm, efficient co-loading of DTX and siRNA, and pH-responsive cargo release, while protecting the siRNA from degradation in serum. Also, DTX/siRNA/cRGD-PLPs maintained homogeneous size distributions over the storage period and induced minimal hemoglobin release, with hemolysis rates remaining below safety threshold. These liposomes demonstrated enhanced, time-dependent uptake into TNBC cell lines HCC1937 and MDA-MB-231. In vitro , the DTX/siRNA/cRGD-PLPs formulation was significantly more effective at inhibiting cell viability, proliferation, migration, and invasion, and at inducing apoptosis, compared to the free drug combinations and other controls. Moreover, the dual-payload co-delivery liposomes (DTX/siRNA/cRGD-PLPs) exerted superior anti-tumor effects relative to single-agent formulations. In an MDA-MB-231 xenograft mouse model, the liposomal treatment was well-tolerated and resulted in marked tumor growth inhibition, which was associated with reduced cell proliferation (Ki67) and increased apoptosis (Caspase-3) within the tumor tissue. This targeted co-delivery system shows significant potential for improving TNBC treatment by synergistically enhancing therapeutic efficacy and overcoming chemoresistance.
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Asian Journal of Pharmaceutical Sciences
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2026
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IF 12.6
Xinying Wang,Xianlu Zhang,Zixuan Jiao,Shipeng Ning,Hanping Wang,Hui Liu,Lifen He,Haonan Li,Mingzhong Li,Kaiyuan Wang,Zhonggui He,You Pan
The treatment of triple-negative breast cancer (TNBC) is significantly hampered by its immunosuppressive tumor microenvironment and limited T-cell infiltration. Activating the STING pathway presents a promising therapeutic avenue due to its potential to trigger a robust innate immune response and remodel the immunosuppressive landscape, thereby sensitizing tumors to immunotherapy. To harness this potential, we developed an exosome-mimetic nanoplatform (EMMDs). EMMDs is fabricated by co-loading a disulfide-linked docetaxel prodrug (DTX-SS-PA) and the STING agonist MSA-2 into polymeric micelles and further decorated with homotypic tumor cell-derived exosomal membrane (EM). This biomimetic design confers superior tumor-targeting capability. Upon reaching the tumor site, the prodrug is specifically activated to release cytotoxic docetaxel (DTX), while MSA-2 is concurrently released to potently activate the STING pathway. This dual action initiates a powerful antitumor immune response and reverses immunosuppression, leading to a synergistic chemo-immunotherapeutic outcome. In the murine TNBC model, EMMDs demonstrated remarkable antitumor efficacy, obviously provoking a robust STING-mediated type I interferon response and inhibiting tumor growth. This work presents a promising biomimetic strategy for remodeling the tumor immune microenvironment via efficient STING activation.
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ACTA BIOCHIMICA ET BIOPHYSICA SINICA
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2026
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IF 4.5
Song Hu,Linghui Kong,Mo Chen,Cheng Teng,Ying Zhao,Xiaohong Yuan,Shunv Cai,Xiaoyan Zhu,Pingbo Xu
The docetaxel-carboplatin (TCb) combination is a widely used neoadjuvant chemotherapy regimen, yet its clinical application is frequently accompanied by hepatotoxicity and drug-induced liver injury (DILI). However, the underlying molecular mechanisms remain incompletely understood. This study investigates the role of cGAS-STING-mediated autophagy in TCb-induced DILI. A TCb-induced DILI mouse model is established by intraperitoneal administration of docetaxel (10 mg/kg) and carboplatin (50 mg/kg) once weekly for two weeks, alongside an in vitro AML12 hepatocyte model (docetaxel 20 μM + carboplatin 100 μM). Liver injury, apoptosis, autophagy, and cGAS-STING signaling are evaluated using histopathological staining, biochemical assays, RT-qPCR, western blotting, immunofluorescence, and immunohistochemistry. TCb treatment induces significant liver injury, as evidenced by elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL), histopathological damage, and increased collagen deposition. TCb markedly promotes hepatocyte apoptosis, characterized by increased expression of Bcl-2 associated X protein (BAX) and decreased expression of Bcl-2. Concomitantly, TCb suppresses basal autophagy, as indicated by p62 accumulation, reduced Beclin-1 expression, decreased LC3-II/I ratio, and diminished autophagosome formation. Mechanistically, TCb robustly activates the cGAS-STING pathway, accompanied by enhanced phosphorylation of TBK1 and IRF3. Notably, pharmacological inhibition of STING with C-176 or siRNA-mediated STING knockdown restores autophagic flux and significantly attenuates TCb-induced apoptosis. Collectively, these findings suggest that sustained activation of the cGAS-STING pathway contributes to TCb-induced DILI by impairing autophagic homeostasis and promoting hepatocyte apoptosis. Targeting cGAS-STING-mediated autophagy represents a potential therapeutic strategy for preventing chemotherapy-associated hepatotoxicity.
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Wang Weilin,Hu Qiaoying,Wu Chunyan,Ding Jiayue,Zhu Chuanxiu,Wen Jiayao,Li Yingchao,Yang Menghan,Wang Yujie,Sun Deqing,Zhai Guangxi,Zhang Yanan
Ferroptosis and sonodynamic therapy (SDT) have both been recognized as powerful weapons in cancer treatment, especially in non-small-cell lung carcinoma (NSCLC) recently. However, the lack of effective sono-sensitizer and ferroptosis regulator limited their usage. In order to overcome the limitation, a novel nanoplatform of DTX-CS/ART/PFCA@RGD (cRCAPD) was fabricated based on SDT and ferroptosis. Nanoparticles, under the action of c(RGDfk) cyclic peptides and their skeleton chondroitin sulfate (CS), could specifically target αvβ3 and CD44 receptors, respectively, thereby targeting tumor sites. Meanwhile, the peroxy-bridge structure of ART disrupted the intracellular iron homeostasis while generating highly toxic reactive oxygen species (ROS) under the SDT. Docetaxel (DTX) in nanoparticles led to the excellent apoptosis of A549 cells. Oxygen carried by PFCA alleviated the tumor hypoxic microenvironment, downregulated HIF-1α, and provided substrates for SDT. Further, the nanoparticles showed a strong immunogenic cell death (ICD) effect, modulating the number of T cells and dendritic cells in tumor-bearing mice. In summary, the proposed therapeutic strategy based on SDT and ferroptosis holds promising potential for synergistic treatment of lung cancer in future clinical applications. Graphical The alternative text for this image may have been generated using AI.
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ACS Applied Bio Materials
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2025
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IF 4.7
Yang Wang,Dianpeng Li,Min He,Gang Wang,Shulin Zhao
The treatment of non-small cell lung cancer (NSCLC) primarily relies on chemotherapy following surgical intervention. However, many late-stage NSCLC patients exhibit drug resistance and experience significant side effects from current chemotherapy agents, ultimately leading to disease progression. Consequently, the development of strategies to enhance efficacy while minimizing side effects through multimodal synergistic treatment technologies remains challenging. Here, we prepared a stable multifunctional nanocomplex, PLGA@DTX@Fe3+-TA/GOX (PDFTG), which utilizes poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles to encapsulate docetaxel (DTX) as the core component, while a Fe3+-tannic acid (TA) nanonetwork serves as the outer coating. Additionally, interactions between polyphenols and proteins facilitate the loading of glucose oxidase (GOX). After intravenous injection, PDFTG selectively accumulates in the tumor region, subsequently releasing Fe3+, TA, DTX, and GOX, thereby remodeling the tumor microenvironment. Following this process, Fe3+ is reduced to Fe2+ by TA, leading to mitochondrial damage in cancer cells and resulting in an increase in O2 content. This increase promotes the GOX-catalyzed glucose oxidation reaction that generates gluconic acid and H2O2, initiating starvation therapy. The gluconic acid enhances the acidity of the microenvironment, further promoting the release of PDFTG nanoparticles and enhancing the accumulation of H2O2 within the cell. The accumulated H2O2 reacts with Fe2+ in a strongly acidic environment, leading to the of hydroxyl free radicals that initiate chemical dynamic therapy (CDT). Moreover, mitochondrial damage results in a reduction of adenosine triphosphate levels, which decreases the expression of P-glycoprotein, thereby reversing DTX resistance and producing potent multimodal synergistic antitumor effects. Multimode treatment strategies for reshaping the tumor microenvironment offer an approach with significant clinical application potential for the efficient treatment of NSCLC.
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International Journal of Pharmaceutics-X
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2026
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IF 6.4
Yangyang Song,Xue Tan,Kai Yu,Yue Wang,Jixue Wang
Docetaxel (DTX) remains the first-line chemotherapeutic for advanced prostate cancer, however, its therapeutic efficacy remains limited by poor aqueous solubility, rapid systemic clearance, and severe dose-dependent toxicity. To overcome these constraints, we developed a PEGylated, disulfide-bridged hierarchical mesoporous silica nanocarrier (PEG–HMS) as a redox-sensitive delivery system for DTX (PEG–HMS–DTX). The nanostructure was fabricated by integrating disulfide-containing organosilanes into the silica framework and conjugating thiol-reactive PEG chains, thereby combining long circulation stability with tumor-selective release. Comprehensive physicochemical characterization confirmed uniform spherical morphology, an optimal hydrodynamic size (∼40–50 nm), attenuated surface charge following PEGylation, and high colloidal stability in physiological media, while disulfide linkages enabled responsive structural changes under reductive conditions. Drug release was minimal under physiological conditions (<30% at 72 h) but markedly accelerated in the presence of glutathione (∼60% at 72 h). Compared with free DTX or non-PEGylated carriers, PEG-HMS-DTX exhibited stronger cellular uptake and enhanced cytotoxicity in RM-1 prostate cancer cells. In tumor-bearing mice, PEG-HMS-DTX achieved superior tumor accumulation (peak at ∼12 h), pronounced tumor growth inhibition (>70%), minimal systemic toxicity, and elevated apoptosis characterized by increased cleaved caspase-3 and reduced PCNA/Bcl-2 expression. Collectively, this “stable-in-circulation, trigger-in-tumor” platform substantially improves intratumoral DTX delivery and apoptosis-driven antitumor efficacy, while maintaining systemic safety. These findings highlight PEG-HMS-DTX as a promising and generalizable strategy for prostate cancer chemotherapy, warranting further pharmacokinetic, immunogenicity, and GLP toxicology studies to support translational advancement.
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MICROCHEMICAL JOURNAL
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2026
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IF 5.1
Sai-Nan Qin,Yi-Xue Zhang,Yi-Jie Cao,Ting Wan,Yi-Yang Zhou,Shan-Shan Su,Yu-Qiong Guo,Jian-Jun Sun,Kalle Salminen
Cisplatin (DDP), as a broad-spectrum anticancer drug, requires dynamic monitoring of its blood concentration and intervention in its dosage administration to balance efficacy and safety due to significant individual differences in its metabolism, side effects, and resistance in different patients. However, rapid and robust methods for monitoring and quantifying DDP in complex biological fluids are still lacking. This work presents an electrochemical aptamer-based ( E -AB) sensor for rapid measurement of DDP concentration in blood. In which capture probe aptamers were designed constructed by visualizing and analyzing their binding pockets, followed by molecular docking and circular dichroism to screen the aptamer Apt25, which has a small binding energy and a large conformational change, for use in the construction of the sensor. In the presence of DDP, the aptamer undergoes a conformational change at the electrode interface, altering the electron transfer rate of the electroactive label to detect DDP concentration variations. After systematically using electrochemical techniques to optimize the sensor testing conditions, the sensor can directly analyze and detect DDP in urine and blood with a measurement range of 0.001–2 mM and a detection limit of 1 μM, which satisfies the needs of clinical testing. The spiked recoveries in different biological samples were 80.8–110% and 79–115.2%, respectively. In addition, the sensor has sufficient selectivity and stability, which is expected to enable real-time monitoring of DDP concentration for dosage adjustment and improvement of drug bioavailability at the clinical site.
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JOURNAL OF CONTROLLED RELEASE
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2023
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IF 10.8
Rengui Xu,Honglian Guo,Xiuli Chen,Jiarong Xu,Yusheng Gong,Peng Cao,Chunyu Wei,Fei Xiao,Di Wu,Wei Chen,Lin Wang,Zheng Wang
Locoregional therapy has attracted increasing attention for subcutaneous tumors owing to its merits of minimally invasive operation and negligible systematic toxicity. However, to accelerate clinical translation, further promotions in deep-seated penetration, temporal-spatial controllability, personalized adaptability, as well as easy operation are still urgently needed. This work proposed a self-heating-cooking-package-inspired hydrothermally responsive multi-round acturable microneedle (HRMAM) system, which loaded docetaxel (DTX) in the polycaprolactone (PCL), to serve as deeply penetrable, hydrothermal-chemotherapy synergetic, on-demand and self-service anti-tumor treatment. The optimized hydrothermally responsive formulation served as base components for water-based self-heating responsive drug release with synergistic anti-tumor thermal therapy, and simultaneously in combination with well-designed grooved-structure needle tips for directional deep delivery and enhanced transfer efficiency. To satisfy spatial precision and flexible controllability, this engineering-based detachable HRMAM system was divided into three relatively independent segments, which were fitted perfectly with an original-designed applicator for ensuring easy operation in a smart self-service manner. Impressively, the HRMAM system achieved encouraging tumor growth inhibition of 75.11% and 72.29% in animal model of melanomas and breast carcinoma , respectively, much higher than those of other groups receiving traditional treatment, without obvious side effects. It was anticipated that the HRMAM system would manifest great promise to combat unreachable and deep-seated subcutaneous tumors, bellowing clinical values upon locoregional therapy products with high efficiency, low toxicity, flexible controllability, temporal-spatial precision, easy operation, as well as patient's painless, comfort and compliance.
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OPTICAL MATERIALS
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2023
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IF 3.9
Fang Fang,Shaohua Zhang,Chaofan Chen,Xueying Wang,Chuannan Luo,Qin Wei
Curcumin can be used to treat cancer diseases, however the side effects of excessive use are serious, and the dosage of curcumin should be accurately controlled. In this study, a fluorescence nanosensor using carbon quantum dots (N,S-CQD) embedded multifunctional molecularly imprinted polymer (N,S-CQD@MIP) composite was developed as a probe for the detection of curcumin. The N,S-CQD@MIP was synthesized by sol-gel method and found a maximum emission peak at 430 nm. The curcumin can be binded selectively by the specific interaction between recognition sites and template molecules. The corresponding sensing mechanism of N,S-CQD@MIP for the detection of curcumin is the result of fluorescence inner filter effect and the static quenching effect. The fluorescence nanosensor using N,S-CQD@MIP for the curcumin detection has a good linear relationship in the range of 0.339–136.0 μM, and the corresponding detection limit is as low as 1.357 nM. This method has been applied to detect the curcumin in real samples with the recoveries of 97.6–103.7%. These results indicate that N,S-CQD@MIP are potential sensing materials for curcumin detection.
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