Advanced Science
·
2026
·
IF 14.1
Bo Chen,Yangyi Wang,Tingting Li,Changqing Guo,Zhe Xie,Zhixian Zhang,Xinghua Han,Wei Wang,Jian Wang,Xiaopeng Ma,Yuanzeng Min
Drug resistance in solid tumors has emerged as a critical challenge, with limited effective therapeutic options available. In this study, we find that chemotherapy induces an increased tumor neoantigens burden (TNB) in breast cancer patients and both non‐resistant and chemo‐resistant triple‐negative breast cancer 4T1 tumor‐bearing mice. Consistently, proteomic analysis reveals that tumor antigens derived from in vitro chemotherapy‐treated paclitaxel (PTX)‐resistant 4T1 cells (chemo‐rAg) are enriched in damage‐associated molecular patterns and neoantigens, highlighting their potential to elicit antitumor immunity against chemo‐resistant tumors. Based on these findings, we utilize the feature of PTX resistance and develop a nanovaccine incorporating chemo‐rAg and a prodrug of a toll‐like receptor 7 (TLR7) agonist. In preclinical mouse models, the nanovaccine effectively suppresses PTX‐resistant 4T1 tumor growth, and it also reverses the innate resistance of immune checkpoint inhibitors. Notably, the therapeutic benefit of the nanovaccine is augmented by chemotherapy, which facilitates in situ release of tumor antigens. These results suggest that a chemo‐rAg‐based nanovaccine represents a promising strategy based on the ′like cures like' principle to overcome drug resistance by utilizing the characteristic of the drug resistance itself. In the murine triple‐negative breast cancer (TNBC) model, chemotherapy effectively increases tumor neoantigen burden (TNB). Here, the study constructs a liposomal nanovaccine using antigens derived from in vitro chemotherapy‐treated paclitaxel‐resistant TNBC 4T1 cells. The combination of the nanovaccine and immune checkpoint inhibitor (ICI) potently suppresses the growth of subcutaneously implanted paclitaxel‐resistant 4T1 tumors, effectively overcoming the drug resistance.
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ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Ke Li,Zhengxiang Wang,Zaigang Zhou,Huan Ding,Sheng Wu,Yuan Li,Jianliang Shen
Cuproptosis, an emerging form of mitochondrial cell death triggered by copper overload, has attracted increasing attention in tumor therapy. However, clinically available copper delivery agents lack tumor mitochondrial targeting specificity, which markedly restricts their clinical application due to their possible hepatotoxicity and nephrotoxicity. Here, we design a stepwise-targeted nanocuproptosis (MTPY-Cu@Alb), capable of sequentially targeting both tumor mitochondria to selectively induce cuproptosis. Strikingly, MTPY-Cu@Alb triggers nanocuproptosis at only 1/1000 the dosage of free copper ions, which then simultaneously reverses tumor immune tolerance mediated by copper homeostasis. Mechanistically, MTPY-Cu@Alb precisely induces cuproptosis and downregulates the immune checkpoints Cluster of Differentiation 276 (CD276) and Cluster of Differentiation 47 (CD47). By reducing these immune checkpoints, MTPY-Cu@Alb effectively reverses adaptive (CD276-associated) and innate (CD47-associated) immune resistance, thereby promoting T-cell infiltration, enhancing cytotoxic activity, and increasing macrophage phagocytosis of tumor cells. Functionally, MTPY-Cu@Alb-induced nanocuproptosis not only exhibits potent antitumor efficacy but also overcomes the chemotherapy-induced upregulation of immune checkpoints and disrupts chemotherapy-mediated resistance to cuproptosis, thereby achieving synergistic antitumor activity with chemotherapy. Collectively, this work highlights the potent ability of using MTPY-Cu@Alb as a promising mitochondria-targeted nanocuproptosis to reverse tumor immune resistance by inhibiting CD276 and CD47 expression and enhancing responsiveness to chemotherapy.
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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 DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2026
·
IF 4.9
Yong Wang,Jie Pi,Yuzi Zhao,Qingzhen Xie
Ovarian cancer (OC) remains a highly lethal malignancy with substantial clinical challenges, including severe side effects and acquired resistance associated with conventional chemotherapeutics such as carboplatin (CBP). To address these limitations, we developed a dual-therapy nanoplatform by co-loading CBP and hyaluronic acid (HA) onto hyaluronic acid-functionalized manganese-based nanoparticles via a facile incubation method. The resulting CBP@HMnO 2 @HA nanoparticles exhibited a uniform hydrodynamic diameter of 210.3 nm and a zeta potential of −31.2 mV, enabling effective tumor-targeted delivery for combined chemotherapy and chemodynamic therapy. In vitro studies demonstrated that the nanoparticles markedly enhanced reactive oxygen species (ROS) generation via peroxidase-like activity and triggered immunogenic cell death (ICD), as evidenced by the pronounced release of damage-associated molecular patterns (DAMPs) including ATP and HMGB1. In vivo biodistribution studies showed significant tumor-specific accumulation within 24 h post-injection, leading to potent suppression of tumor growth. Mechanistically, the antitumor efficacy was associated with activation of the cGAS-STING signaling pathway. Collectively, these results indicate that CBP@HMnO 2 @HA nanoparticles possess integrated chemotherapeutic, chemodynamic, and robust catalytic functionalities, offering a promising multimodal nanotherapeutic strategy for the treatment of ovarian cancer.
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MICROCHEMICAL JOURNAL
·
2026
·
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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Bioactive Materials
·
2022
·
IF 16.874
Yi Xiao,Haomin Yi,Jingzhi Zhu,Suhua Chen,Guofang Wang,Yilong Liao,Yuanyuan Lei,Liyin Chen,Xingcai Zhang,Fangfu Ye
Toxicity assessment is a major problem in pharmaceutical candidates and industry chemicals development. However, due to the lack of practical analytical methods for DNA adduct analysis, the safety evaluation of drug and industry chemicals was severely limited. Here, we develop a DNAzyme-based method to detect DNA adduct damage for toxicity assessment of drugs and chemicals. Among 18 structural variants of G4 DNAzyme, EA2 DNAzyme exhibits an obvious DNA damaging effect of styrene oxide (SO) due to its unstable structure. The covalent binding of SO to DNAzyme disrupts the Hoogsteen hydrogen bonding sites of G-plane guanines and affects the formation of the G4 quadruplex. DNA damage chemicals reduce the peroxidase activity of the G4 DNAzyme to monitor the DNA adduct damage by disrupting the structural integrity of the G4 DNAzyme. Our method for genotoxic assessment of pharmaceutical candidates and industrial chemicals can elucidate the complex chemical pathways leading to toxicity, predict toxic effects of chemicals, and evaluate possible risks to human health.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-19
·
IF 10.2
Wang Yaotai,Zhang Zhong,Ren Li,Luo Yong,Wang Qi,Zou Jianzhong
Focused ultrasound ablation surgery (FUAS) is a novel therapy with a wide range of potential applications. However, synergists are crucial to the therapy process due to the ultrasonic energy's attenuation properties. As a result of the complex hypoxic environment in the tumor area and many factors, the existing synergists have limitations such as weak targeting, single imaging mode, and easy tumor recurrence after treatment. Because of the above deficiencies, this study intends to construct bio-targeted oxygen production probes consisting of Bifidobacterium that naturally target the hypoxia region of the tumor and multi-functional oxygen-producing nanoparticles equipped with IR780, perfluorohexane (PFH), CBP (carboplatin), and oxygen. The probes are expected to achieve targeted and synergistic FUAS therapy and dual-mode imaging to mediate tumor diagnosis and treatment. The oxygen and drugs carried in it are accurately released after FUAS stimulation, which is expected to alleviate tumor hypoxia, avoid tumor drug resistance, improve the effect of chemotherapy, and realize FUAS combined with chemotherapy antitumor therapy. This strategy is expected to make up for the deficiencies of existing synergists, improve the effectiveness and safety of treatment, and provide the foundation for future tumor therapy progress.Graphical Abstract
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Translational Cancer Research
·
2021
·
IF 1.241
Dong Luo,Wenzhi Chen,Wei Wang,Junlin Chen,Haopeng Xu,Jinyun Chen,Yan Wang
Background Our team has previously reported that low intensity pulsed ultrasound (LIPUS) can alleviate myelosuppression in rats induced by single chemotherapy drugs. But in clinics, chemotherapy is often performed with multiple drugs simultaneously. To be closer to the clinical status quo, this experiment was designed to show whether it was the same effect of LIPUS on myelosuppression caused by combination therapy of chemotherapy drugs. Methods The rat model of myelosuppression was established by continuous injection of paclitaxel and carboplatin for 4 days. These myelosuppressive rats were randomly divided into LIPUS group (n=40) and control group (n=40). The LIPUS group was given continuous LIPUS irradiation for 7 days, while the control group was given sham irradiation (no energy output). The evaluation of blood cells counts, Hematoxylin-Eosin staining (H&E staining), scanning electron microscopy, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (qPCR) was then performed. Results The results showed in the LIPUS group the blood cells count, hematopoietic tissue of bone marrow, the colonies formed from adhering of bone marrow stromal cells, levels of hematopoietic regulators and adhesion molecules all increased (LIPUS group vs. control group, P<0.05). Conclusions The results indicated that LIPUS can relieve myelosuppression induced by combined treatment of paclitaxel and carboplatin. The mechanisms may be LIPUS can increase the levels of hematopoietic regulators and adhesion molecules.
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ONCOLOGY REPORTS
·
2020
·Vol. 44
·期 3
·927-938
·
IF 3.417
Songhui Zhou,Ruicheng Wang,Hong Xiao
The resistance of cancer cells to carboplatin restricts their efficacy in the clinical setting, and a solution to reverse the resistance is urgently required for the treatment of ovarian cancer. An increasing number of studies have found associations between obesity and the incidence, and mortality rates of female cancer. However, the association between adipocytes and the resistance of ovarian cancer has rarely been reported. Based on this, the present study first revealed the inductive effect of adipocytes on the resistance of ovarian cancer to carboplatin using in vivo and in vitro experiments. Subsequently, it was identified that the angiopoietin‑like 4 (ANGPTL4) secreted by adipocytes played a vital role in the resistance of ovarian cancer using bioinformatics analysis, cellular and molecular biological experiments, as well as forward and backward validation. The glycosylated ANGPTL4 protein could bind with integrin α5β1 on the surface of ovarian cancer cells; following which, it could activate the c‑myc/NF‑κB pathway and stimulate the expression of the antiapoptotic protein Bcl‑xL, as well as the ABC transporter family members ABCB1, ABCC1 and ABCG2. Thus, inducing the resistance of ovarian cancer to carboplatin. In conclusion, targeting the adipocyte‑derived ANGPTL4 combined with the application of carboplatin contributes to the clinical treatment for ovarian cancer.
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PLoS One
·
2017
·Vol. 12
·期 11
·e0186184
·
IF 2.806
Tingyu Yu,Jiao Lin,Jin Zhao,Wei Huang,Lingwen Zeng,Zhiyuan Fang,Ning Xu
The analysis of intracellular ATP can reveal the response of cells to different treatments and is important for individualized medicine. In the present study, we developed a cell penetrating peptides (CPPs) tagged luciferase (TAT-LUC) for tumor chemosensitivity assay. The activity of recombinant TAT-LUC was evaluated using ATP standard solution and tumor cells. This recombinant TAT-LUC was then used for the analysis of sensitivity index (SI) of four strains of tumor cells. The results showed that TAT-LUC could detect less than 10 nM extracellular ATP with a strong correlation between the luminescence intensity and the ATP content (R 2 = 0.994). Without cell lysis, the detection limit for intracellular ATP analysis was 40 tumor cells. Furthermore, chemosensitivity of four strains of tumor cells (Skov-3/DDP, A549/DDP, MDA-MB-231, Huh-7) was determined by this assay successfully. The cell penetration ability of TAT-LUC enables the assay not only to reflect drug resistance of tumor cells real-timely but also to minimize the test time, which can be a valuable aid for personalized cancer chemotherapy.
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INORGANIC CHEMISTRY COMMUNICATIONS
·
2024
·
IF 4.4
Juan Chen,Liuqing Huang,Xiaobing Yang,Yan Li,Tong Lin,Chentong Zhang,Jintang Li,Xuetao Luo
The covalent functionalization of the zeolitic imidazolate framework (ZIF) is rapidly progressing and is being exploited as a nanoplatform for antitumor drug delivery to improve tumor targeting and drug release. Here, a novel nanoplatform strategy was developed by encapsulating Carboplatin (CBP) in ZIF-90 nanospheres (NPs) to obtain CBP@ZIF-90 NPs and then, modifying folate-terminated methoxypoly(ethylene glycol) (FA-PEG-NH 2 ) on the aldehyde group of ZIF-90 to form CBP@ZIF-90-NPF NPs with acid-sensitive Schiff base bond. The research results indicate that the yield of ZIF-90 was 72.77 ± 0.27 %, and the encapsulation efficiency and the loading content of CBP@ZIF-90 were 45.22 ± 0.49 % and 24.65 ± 0.34 %, respectively. The size of CBP@ZIF-90-NPF was 107.7 ± 1.7 nm in monodispersity with a single crystalline dodecahedral structure. Furthermore, the in vitro release behavior study revealed the sustained-release and the pH-responsive dissociation properties of the NPs. Only 6.84 % of CBP was released from the nanocarrier under physiological pH conditions for 48 h, while the release from the tumor microenvironment was 92.89 %. In addition, the cellular uptake result clearly showed that most of the FA-PEG-NH 2 modified NPs exhibited specific selectivity in tumor cell nuclei. Finally, the cell counting kit-8 (CCK8) assay based on human ovarian cancer cell line (OVCAR-3) and human normal ovarian epithelial (IOSE-80) cell line obviously indicated that the ZIF-90 NPs had good biocompatibility and minimal cytotoxicity, as well as the high inhibition efficiency of the CBP@ZIF-90-NPF NPs meant that a much higher amount of CBP was transferred into the folate receptor (FR)-overexpressed ovarian cancer cells via FR mediated endocytosis. These results suggest that ZIF-90-NPF NPs could be an ideal targeted drug delivery vehicle for CBP, serving as a promising strategy for ovarian cancer treatment.
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BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
·
2025
·
IF 2.7
Weibin Luo,Zhengyuan Yang,Shihua Gao,Bin Peng
Lung carcinoma is one of the most severe types of cancer, characterized by a dismal prognosis and low overall survival rate, primarily due to late diagnosis and the ineffectiveness of standard treatments. Hence, this study aimed to develop bevacizumab (BZ)-functionalized albumin (BS)-clad, carboplatin (CP)-loaded hollow mesoporous selenium (HMS) nanoparticles (BBHMSC) for the targeted administration of HER2+ Calu-3 lung cancer. The structural properties of these nanoparticles were characterized using transmission electron microscopy (TEM). Cell viability was assessed using the 3-[4,5-dimethylthiazol-2-yl]- 2,5-diphenyltetrazolium bromide (MTT) assay. The images were obtained from fluorescence microscopy. The in vitro characterization of the pharmacological characteristics indicated that BBHMSC was uniformly disseminated, with a particle size of 171.52 ± 4.3 nm. In vitro release tests demonstrated that BBHMSC proficiently regulated the release of CP in the tumor microenvironment (elevated glutathione concentration), achieving a cumulative release rate of 87.1 ± 3.9% over 48 h. A cellular uptake assay validated that BBHMSC has an effective tumor-targeting capability. In vitro cell investigations, MTT studies, have shown that BBHMSC dramatically suppresses proliferation and growth. Further, BBHMSC enhances the apoptosis of HER2+ Calu-3 cells by fluorescence and flow cytometry methods. The data indicate that BBHMSC may be an effective targeted therapy for HER2+ti lung cancer.
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