JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Yunfan Li,Kaiwen Bao,Renzheng Huan,Tian Wang,Ya Wang,Shuai Wu,Xin Chen,Jiashang Huang,Li Zhu,Jianshu Li,Haifeng Yang,Wei Wu
Glioblastoma (GBM) is one of the most aggressive malignancies of the central nervous system. Gemcitabine (GEM), a pyrimidine analogue with broad-spectrum anticancer activity, can activate the cGAS-STING pathway and alleviate the immunosuppressive microenvironment of GBM. However, its clinical application is hampered by the formidable challenge of crossing the blood-brain barrier (BBB) and accumulating at the tumor lesion. Herein, a dual-responsive biomimetic nanoprodrug (RMM@GEM NPs) was exploited to enhance the efficient BBB penetration and target cargo delivery by functionalization of glioblastoma cell membranes (MM) camouflaging and further targeting peptide RAP modification. After its selective accumulation at glioma lesion, RMM@GEM NPs accelerates GEM release under the tumor pathological stimuli of reactive oxygen species (ROS) and acidic microenvironment to robustly activate the STING signaling cascades (increased p-STING, p-TBK1, p-IRF3, and p-NF-κB). Simultaneously, cyclodextrin-mediated cholesterol depletion further suppresses PD-L1 expression and alleviates T-cell exhaustion. These findings highlight RMM@GEM NPs as a promising strategy to enhance immune responses in “cold” tumor, providing a potential candidate for efficient and safe immunotherapy in GBM.
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International Journal of Refrigeration
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2026
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IF 4
Yukun Cao,Xin Li,Jing Shen,Shanshan Xie,Haoyang Lin,Yuling Luo,Xinli Zhou
Optimized cryoablation protocol minimizes the sublethal zone in PDAC models. • High cooling rates, extended holding, and dual cycles elevate lethal thresholds. • Lethal temperatures are shifted upward to −20 °C (PANC-1) and −15 °C (BxPC-3). • First study combining cryoablation with Nab-paclitaxel/Gemcitabine regimen. Incomplete tumor ablation within the peripheral sublethal zone remains a critical limitation of cryoablation for pancreatic ductal adenocarcinoma (PDAC). This study aimed to enhance ablative efficacy by optimizing freezing parameters and integrating combination chemotherapy. A GelMA-based 3D tissue model was initially employed to characterize thermal gradients and define lethal thresholds. Subsequently, a programmable freezer simulated sublethal conditions (-10 to -25 °C) to evaluate specific freezing protocols on PANC-1 and BxPC-3 cells. Results demonstrated that an optimized protocol comprising rapid cooling (50 °C min -1 ), extended hold, and dual cycles significantly elevated the effective lethal isotherm. Mechanistic investigation revealed a temperature-dependent shift in cell death modalities: apoptosis predominated at -13 °C, whereas necrosis became dominant at ≤-15 °C. This transition was underpinned by intensified intracellular reactive oxygen species accumulation and mitochondrial depolarization as freezing temperatures decreased. Furthermore, combining cryoablation with gemcitabine-based regimens markedly suppressed post-cryoablation viability. Notably, cryoablation induced a significant chemo sensitizing effect. In PANC-1 cells, low-dose chemotherapy (1/10th of the high dose) achieved efficacy comparable to high-dose regimens at temperatures ≤-13 °C. Conversely, BxPC-3 cells retained dose-sensitivity down to -13 °C. In conclusion, optimizing cryoablation parameters expands the effective ablative zone and synergizes with low-dose chemotherapy via enhanced oxidative stress and mitochondrial dysfunction, offering a promising strategy for PDAC treatment.
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2026
·
IF 5.7
Shuting Han,Jiaru Wang,Jiao Xue,Junjie Miao,Xingyu Liu,Shuhui Yin,Qian Wang,Jing Jin
Chemoresistance is a significant factor in the failure of cancer treatment. Although some chemotherapeutic combination regimens are linked to DNA damage repair processes, the therapeutic potential of TCM-derived small molecules that target these mechanisms is still underexplored. Alloimperatorin (Alloi) has demonstrated the ability to inhibit tumor growth; however, the efficacy and molecular mechanisms of its combination with chemotherapeutic agents are not yet fully understood. Here, we demonstrate that Alloi sensitizes multiple tumor cell lines to gemcitabine (GEM) both in vitro and in vivo. Using functional assays, we confirmed a potent synergistic inhibitory effect of the Alloi-GEM combination, which markedly suppressed pancreatic cancer progression in vivo with minimal adverse effects. By integrating transcriptome sequencing with network pharmacology, we identified downregulation of c-MYC and Nijmegen Breakage Syndrome 1 gene (NBS1) as a key mechanistic event, a finding subsequently validated through multiple assays. Mechanistically, the Alloi-GEM regimen induces sustained DNA damage via disruption of the c-MYC-NBS1 axis, thereby impairing the DNA damage response pathway. Collectively, our findings establish that Alloi enhances tumor sensitivity to GEM through modulation of the c-MYC/NBS1 axis and identify this combinatorial strategy as a promising approach for cancer treatment. Alloi enhances the antitumor effect of GEM by suppressing the c-MYC/NBS1 axis. Downregulation of c-MYC reduces NBS1 expression and impairs MRN complex-mediated DNA damage response signaling, including ATM/CHK2 activation and DNA repair. As a result, GEM-induced DNA damage is sustained, ultimately promoting tumor cell death. Download: Download high-res image (238KB) Download: Download full-size image
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Chengxun Li,Fei Chen,Jianing Wu,Jun Ren,Yingzhu Li,Shengjie Li,Zuguang Xia
Antibody drug conjugates (ADCs) offer targeted cancer therapy but face limitations in drug loading, stability, and immune modulation. Here, antibody DNA nanostructure conjugates (ADNCs) is reported as a next-generation platform that overcomes these challenges. By leveraging the programmable architecture of DNA nanostructures, ADNCs achieve high, tunable drug payloads without inducing antibody aggregation—a major drawback of conventional ADCs. In CT26 cells, gemcitabine-loaded ADNCs trigger dual cell death pathways—caspase-3-mediated apoptosis and RIP3-mediated necroptosis—enhancing tumor cell killing. In the CT26 syngeneic model, ADNCs suppress tumor growth with no observable toxicity and, notably, activate anti-tumor immunity without upregulating PD-1, suggesting avoidance of T-cell exhaustion. Critically, ADNCs maintain efficacy in patient-derived xenograft (PDX) models despite tumor heterogeneity. The study presents a novel, stable, and scalable antibody-drug conjugate (ADC)-inspired platform that integrates high payload delivery capacity with enhanced and adjustable drug-loading capabilities—characteristics that are seldom achieved in existing ADC technologies—thereby demonstrating translational potential for applications in precision oncology.
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CHEMICAL ENGINEERING JOURNAL
·
2026
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IF 12.5
Jiaming Zhang,Xinyu Lou,Xiaolan Xu,Yingchao Li,Chenxia Bai,Qing Yan,Yanfang Wang,Yixiu Zhai,Jingdong Xiao,Mengchi Sun,Yinghou Wang,Jin Sun,Tianhong Zhang,Qikun Jiang
Chemotherapy is an important strategy in cancer treatment, and harnessing the immunomodulatory potential of chemotherapeutic agents presents novel opportunities for chemoimmunotherapy. The oxaliplatin (OXA) and gemcitabine (GEM) regimen, a clinically established protocol for solid tumors, primarily exerts therapeutic effects through synergistic cytotoxicity, with emerging evidence supporting its ancillary immune-modulating properties. However, intravenous administration is frequently associated with systemic toxicity and impedes precise control of drug ratios within the tumor. Furthermore, GEM undergoes rapid enzymatic degradation by cytidine deaminase (CDA), which is highly expressed in both tumor cells and intratumoral microbiota, compromising its efficacy and disrupting the therapeutic equilibrium with OXA. To overcome these limitations, we developed a sodium alginate (ALG)-based in situ hydrogel system for co-delivery of OXA, GEM, and the CDA inhibitor cedazuridine (CDZ) in a ratio-locked design. Following intratumoral injection, ALG underwent Ca 2+ -triggered gelation, facilitating localized drug retention and sustained synchronized release to mitigate off-target toxicity. CDZ enhanced the metabolic stability of GEM, maintaining the optimal GEM/OXA ratio. Concurrently, beyond cytotoxic synergy, OXA-triggered immunogenic cell death and GEM-driven regulatory T-cell depletion collectively enhance antitumor immunity. This ratio-locked localized delivery platform, integrated with metabolic stabilization, enables precise regimen control to achieve safe and potent chemoimmunotherapy.
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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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Biomedical Materials
·
2023
·Vol. 18
·期 3
·035010
·
IF 4
Fu Zhang,Zhuo Yao,Piaopiao Jin,Mengqiu Xu,Qida Hu,Yuxuan Chen,Risheng Que,Tingbo Liang
Gemcitabine (Gem) has been recommended as a first-line clinical chemotherapeutics for pancreatic ductal adenocarcinoma (PDAC) treatment. Gem treatment could generate chemoresistance associated with abnormal expressions of multiple miRNAs. In the PDAC setting, miRNA-21 (miR-21) overexpression is an important contributing factor of inducing Gem chemoresistance. Inhibition of miR-21 can significantly increase Gem chemosensitivity, which requires an efficient delivery platform to conduct combinational Gem and miR-21 siRNA (miR-21i) therapy. Herein, we synthesized a tumor microenvironment (TME) stimuli-responsive poly(beta-amino ester)s (PBAE)-based polymer nano-prodrug (miR-21i@HA-Gem-SS-P12) that could co-deliver miR-21 siRNA and Gem. The disulfide linkages conjugating GEM onto PBAE can be triggered by elevated reduction stimulus in TME to release the cargo Gem. The hyaluronic acid (HA) fabrication further improved the drug accumulation at the tumor site. Benefiting from the multiple functional improvements and synergism between Gem and miR-21i, the miR-21i@HA-Gem-SS-P12 nano-prodrugs displayed superior tumor inhibition in PDAC in vitro and in vivo. This study established an effective stimuli-responsive nano-prodrug strategy for cooperative treatment with small molecule agents and nucleotide modulators in PDAC.
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FITOTERAPIA
·
2023
·
IF 3.4
Nan Zhang,Junwei Zhang,Weiqi Cui,Deqiao Wu,Jingxian Zhang,Bo Wei,Lingbo Qu,Xia Xu
Artemisia argyi H.Lév. & Vaniot, a traditional Chinese medicine with a history spanning over two millennia, has been extensively used in folk medicine to treat dysmenorrhea, uterine bleeding and inflammation. Recent studies have demonstrated that the essential oil extracted from Artemisia argyi H.Lév. & Vaniot, known as AAEO, exhibits significant anti-tumor properties against liver and lung cancers. There is a scarcity of research on the potential impact of AAEO on pancreatic cancer (PC) cells. In this study, UPLC-MS/MS-based metabolomics method was established to evaluate the effect of AAEO on the proliferation of PC cells. The differential compounds included 5-oxoproline, glutamate, γ-glutamylcysteine, glutathione, arachidonic acid, adrenal acid and linoleic acid were detected by metabolomics, enriching in the γ-glutamyl cycle and polyunsaturated fatty acid metabolism, which were closely related to ferroptosis. Meanwhile, AAEO dramatically increased the levels of intracellular iron ion via up-regulation of TFR1, augmented reactive oxygen species and malondialdehyde in a dose-dependent manner by down-regulation of γ-glutamyl cycle through decreasing expressions of SLC7A11. Additionally, β-caryophyllene oxide, one of the main components of AAEO, could covalently bind to Cys in SW1990 cells to form a conjugate Cpo-Cys, resulting in the inhibition of glutathione synthesis. Importantly, the ferroptosis inhibitor deferoxamine significantly blocked the inhibitory effect of AAEO on SW1990 cells. Meanwhile, β-caryophyllene oxide, dihydro-β-ionone and α-bisabolol had strong binding force with GPX4, SLC7A11 and TFR1, respectively. These findings showed that AAEO induced ferroptosis via regulation of γ-glutamyl cycle by SLC7A11 and iron disorders by TFR1. Our study discovered AAEO as a potential therapeutic approach to induce ferroptosis to prevent or treat PC.
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JOURNAL OF CHROMATOGRAPHY A
·
2023
·
IF 4.1
Hao Chi,Sheng Tian,Xiu Li,Yuchu Chen,Qiumin Xu,Qixiao Wang,Wenwan Shi,Michael Adu-Frimpong,Shanshan Tong
In order to improve the separation process of affinity chromatography that has silica as the main carrier material, we sought to construct Lipid [email protected] 4B affinity chromatography model. We extracted the lipid rafts from U251 cells with a descaler method and sucrose density gradient centrifugation. Afterwards, it was discovered via immunofluorescence that the lipid rafts contain a large amount of tropomyosin-related kinase A (TrkA) protein. Also, agarose powder in the lyophilised state was pretreated, before the lipid rafts were coupled to the agarose gel in a coupling buffer of alkaline pH. CNBr-Sepharose 4B affinity gel packing was characterised using UV spectrophotometric, immunofluorescence and scanning electron microscopic techniques, wherein and the results showed that the lipid rafts were successfully coupled to the agarose gels. Three compounds were used to verify the specific sorption of Sepharose 4B and CNBr-Sepharose 4B, which showed no specific sorption on the materials. Of note, the prepared Lipid [email protected] 4B agarose gels packed with TrkA-rich target proteins could be successfully validated for the active drug gefitinib with high affinity sorption efficiency and eluted with good recovery and reproducibility. This study broadens the range of affinity chromatography carrier materials and provides a reference for research in active drug screening.
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JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Fu Zhang,Qida Hu,Bowen Li,Yong Huang,Meng Wang,Shiyi Shao,Honglin Tang,Zhuo Yao,Yuan Ping,Tingbo Liang
Pancreatic ductal adenocarcinoma (PDAC) remains to be one of the highest malignant tumors due to its poor chemotherapeutic efficacy and multidrug resistance . A major reason for the failure in chemotherapy is poor drug accumulation into PDAC tumor tissues due to the overexpressed extracellular matrix (ECM) stroma, which forms a major obstacle limiting the deep tissue penetration of chemotherapeutics. Herein, we report a tumor microenvironment (TME)-responsive nanodrug, based on PDAC cell membrane-coated gold nanocages (AuNCs), to co-deliver the chemotherapeutics (GEM) and nitrogen oxide (NO) donor (L-Arg) to enhance drug accumulation and reduce chemoresistance. The high glutathione (GSH) level can trigger the cleavage of the disulfide bond on nanodrug to release GEM . Moreover, the elevated ROS level could activate L-Arg to generate NO, which synergistically facilitate GEM to penetrate into deep tissues by means of vasodilation and normalization of blood vessels in the PDAC tumor tissue. In addition, AuNCs not only serve as a photothermal agent for chemotherapy, but also generate photoacoustic signals to monitor drug accumulation and distribution. As expected, the strategy demonstrates to be remarkable in treating different xenograft mice models, especially in orthotopic and patient-derived xenograft (PDX) models. The current study defines a useful therapeutic tool for treating PDAC tumors.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 12
·6597
·
IF 6.208
Yaowei Guo,Jin Liu,Qinglin Tang,Cuicui Li,Yanying Zhang,Yao Wang,Yanxin Wang,Yupeng Bi,Christopher D. Snow,Matt J. Kipper,Laurence A. Belfiore,Jianguo Tang
The clinical use of anticancer drugs necessitates new technologies for their safe, sensitive, and selective detection. In this article, lanthanide (Eu3+and Tb3+)-loaded γ-cyclodextrin nano-aggregates (ECA and TCA) are reported, which sensitively detects the anticancer drug irinotecan by fluorescence intensity changes. Fluorescent lanthanide (Eu3+and Tb3+) complexes exhibit high fluorescence intensity, narrow and distinct emission bands, long fluorescence lifetime, and insensitivity to photobleaching. However, these lanthanide (Eu3+and Tb3+) complexes are essentially hydrophobic, toxic, and non-biocompatible. Lanthanide (Eu3+and Tb3+) complexes were loaded into naturally hydrophilic γ-cyclodextrin to form fluorescent nano-aggregates. The biological nontoxicity and cytocompatibility of ECA and TCA fluorescent nanoparticles were demonstrated by cytotoxicity experiments. The ECA and TCA fluorescence nanosensors can detect irinotecan selectively and sensitively through the change of fluorescence intensity, with detection limits of 6.80 μM and 2.89 μM, respectively. ECA can safely detect irinotecan in the cellular environment, while TCA can detect irinotecan intracellularly and is suitable for cell labeling.Keywords:lanthanide (Eu3+, Tb3+) complex;γ-cyclodextrin;nano-aggregate;sensing;anticancer drug;irinotecan
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Marine Drugs
·
2022
·Vol. 20
·期 5
·284
·
IF 6.085
Yuting Zhu,Shanhao Han,Jianhui Li,Hongwei Gao,Bo Dong
Marine ascidian is becoming one of the main sources of an antitumor drug that has shown high bioactivity and extensive application in cancer treatment.Halocynthia roretzi, an edible marine sea squirt, has been demonstrated to have various kinds of biological activities, such as anti-diabetic, anti-hypertension, and enhancing immunity. In this study, we reported that aqueous extracts from the edible parts ofH. roretzipresented significantly inhibiting the efficiency on HepG-2 cell viability. The separate mixed compound exhibited strong effects of inhibitory proliferation and induced apoptosis via the generation of ROS along with the concurrent loss of mitochondrial membrane potential on tumor cells. Furthermore, we found that there existed a significantly synergistic effect of the ascidian-extracted compound mixture with the anti-cancer drug doxorubicin. In the presence of the extracts fromH. roretzi, the dose of doxorubicin at the cellular level could be reduced by a half dose. The extracts were further divided by semipreparative-HPLC and the active ingredients were identified as a mixture of fatty amide, which was composed of hexadecanamide, stearamide, and erucamide by UHPLC-MS/MS. Our results suggest that the potential toxicity of ascidianH. roretziin tumor cells, and the compounds extracted fromH. roretzicould be potentially utilized on functional nutraceuticals or as an adjunct in combination with chemotherapy.Keywords:ascidian;Halocynthia roretzi;anti-tumor;drug combination;doxorubicin
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