CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Guanghui Hou,Junmin Qian,Min Guo,Weijun Xu,Jinlei Wang,Yaping Wang,Aili Suo
It is still a huge challenge for concurrent highly efficient loading of chemotherapeutic agent and photosensitizer into single nanocarrier via stimuli-responsive linkages due to their different physicochemical properties and pharmacokinetics . Herein, based on the discovery of unique cisplatin-hydrazide and cisplatin-indocyanine green (ICG) coordination reactions, a multifunctional coordination nanoprodrug, cisplatin/ICG co-loaded hydrazided hyaluronan/bovine serum albumin (HBCI) nanoparticles , was developed by a desolvation-dual coordination process. The nanoprodrug exhibited ultrahigh drug loading efficiency and glutathione/NIR light dual-responsive drug release behavior. In vitro cellular studies demonstrated efficient internalization and apoptosis-inducing ability of the nanoprodrug in HepG2 cells. In vivo results confirmed the efficacious tumor accumulation and biosafety of HBCI nanoprodrug and synergistic effect of HBCI-based combined photodynamic chemotherapy on inhibiting tumor growth. Overall, this work not only provides a novel dual coordination approach for highly efficient loading of cisplatin and ICG but also verifies the therapeutic potential of HBCI nanoprodrug in combating hepatocellular carcinoma.
研究领域:
药学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 33
·6296-6306
·
IF 7.571
Yao Lu,Qingqing Pan,Wenxia Gao,Yuji Pu,Bin He
Platinum-based chemotherapy is widely used to treat various cancers. However, exogenous platinum is likely to cause severe side effects and drug resistance induced by upregulated glutathione (GSH) in cancer cells poses a threat to the management of cancer progression and recurrence. Anticancer copper–organic complexes are excellent candidates to substitute platinum-based chemotherapeutics, exhibiting lower systemic toxicity and even overcoming platinum-based chemotherapy resistance. Here, we report the GSH-resistance of copper(II) bis(diethyldithiocarbamate) (CuET) and its reversal of cisplatin resistance in non-small-cell lung cancer via cuproptosis. Electrochemistry and UV-vis spectroscopy studies demonstrate that CuET possesses a lower reduction potential and the reaction inertness with GSH. Importantly, CuET overcomes the drug resistance of A549/DDP cells and the anticancer effect is hardly affected by intracellular GSH levels. To improve the solubility and bioavailability, bovine serum albumin-stabilized CuET nanoparticles (NPs) are prepared and they have a high drug loading content of 27.5% and excellent physiological stability. In vitro studies manifest that CuET NPs augment the distributions in the cytosol and cytoskeleton, inducing cell death via cuproptosis in A549/DDP cells, which is distinctly different from the apoptosis pattern induced by cisplatin. In vivo antitumor evaluation shows that the nanomedicine has superior biosafety and potent antitumor activity in a cisplatin-resistant tumor model. Our study suggests that copper–organic complex-based nanosystems could be a powerful toolbox to tackle the platinum-based drug resistance and systemic toxicity concerns.
研究领域:
肿瘤学
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药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
CELLS TISSUES ORGANS
·
2022
·
IF 2.208
Zhou Yafu,Yan Jianhua,Chen Huiguo,Zhou Wenwu,Yang Jinsong
GINS subunit complex 4 (GINS4) is fundamental to DNA replication and G1/S phase transition of the cell cycle in eukaryotes. Further, recent studies implied that GINS4 can mediate the progression of several tumors, but its mechanism in lung adenocarcinoma (LUAD) is not clarified. Therefore, the role of GINS4 in LUAD was explored. miR-133a-3p and GINS4 mRNA expression were tested through qRT-PCR. Protein levels of the two genes were assayed by Western blot. Their targeting relationship was predicted and verified by bioinformatics prediction and dual-luciferase analysis. The functions of miR-133a-3p and GINS4 in LUAD were evaluated by Transwell, wound healing, CCK-8, and flow cytometry assays. MTT assay and caspase-3 activity detection were utilized to measure the regulation of miR-133a-3p/GINS4 in the cisplatin sensitivity of LUAD cells. The results showed that GINS4 was highly expressed in LUAD cells (p < 0.05). miR-133a-3p, the upstream gene of GINS4 in LUAD, negatively mediated GINS4 expression. Moreover, overexpressing GINS4 enhanced the proliferative, migratory, and invasive abilities of LUAD cells and inhibited cell apoptosis and the sensitivity to cisplatin, while overexpressing miR-133a-3p caused the contrary results. However, the promoting effects of GINS4 overexpression on LUAD could be offset by miR-133a-3p overexpression. miR-133a-3p could regulate malignant behaviors and cisplatin sensitivity of LUAD cells through negatively regulating GINS4. In conclusion, our findings demonstrated that GINS4 was overexpressed in LUAD and promoted the malignant behavior of LUAD cells. Moreover, miR-133a-3p could negatively regulate GINS4, thereby suppressing the malignant progression and increasing the cisplatin sensitivity of LUAD
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Yan Li,Ke Li,Weihao Zhao,Haodong Wang,Xiaodong Xue,Xianghui Chen,Wantao Li,Peihao Xu,Kexin Wang,Pengfei Liu,Xuefei Tian,Rongguo Fu
Background: As a novel non-apoptotic cell death, ferroptosis has been reported to play a crucial role in acute kidney injury (AKI), especially cisplatin-induced AKI. Valproic acid (VPA), an inhibitor of histone deacetylase (HDAC) 1 and 2, is used as an antiepileptic drug. Consistent with our data, a few studies have demonstrated that VPA protects against kidney injury in several models, but the detailed mechanism remains unclear. Results: In this study, we found that VPA prevents against cisplatin-induced renal injury via regulating glutathione peroxidase 4 (GPX4) and inhibiting ferroptosis. Our results mainly indicated that ferroptosis presented in tubular epithelial cells of AKI humans and cisplatin-induced AKI mice. VPA or ferrostatin-1 (ferroptosis inhibitor, Fer-1) reduced cisplatin-induced AKI functionally and pathologically, which was characterized by reduced serum creatinine, blood urea nitrogen, and tissue damage in mice. Meanwhile, VPA or Fer-1 treatment in both in vivo and in vitro models, decreased cell death, lipid peroxidation, and expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), reversing downregulation of GPX4. In addition, our study in vitro indicated that GPX4 inhibition by siRNA significantly weakened the protective effect of VPA after cisplatin treatment. Conclusion: Ferroptosis plays an essential role in cisplatin-induced AKI and inhibiting ferroptosis through VPA to protect against renal injury is a viable treatment in cisplatin-induced AKI.
研究领域:
药理学
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肾病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Research
·
2026
·
IF 9.6
Bo Liu,Yaqin Tu,Xiangrui Li,Wenting Yu,Wenqing Zou,Wei Tang,Shimin Zong,Songwei Tan,Hongjun Xiao
Cisplatin (CDDP) is a widely used chemotherapeutic agent, but its clinical applications are constrained by ototoxic side effects. Currently, few effective strategies exist to prevent or mitigate CDDP-induced ototoxicity. Rutin is known for its cell-protective effects by reducing oxidative stress and inhibiting apoptosis. However, its limited water solubility and inefficient delivery to the inner ear pose substantial challenges. To address this, rutin is encapsulated in liposomes (Lip-Rutin) for nanoscale drug delivery, leveraging its antioxidant properties. Lip-Rutin markedly attenuates CDDP-induced oxidative stress damage and apoptosis, demonstrating a protective effect on OC-1 cells. The efficacy of Lip-Rutin in safeguarding against CDDP-induced ototoxicity is further validated through in vivo studies. Consequently, Lip-Rutin emerges as a promising novel therapeutic agent for combating CDDP-induced ototoxicity.
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2014
·Vol. 35
·期 24
·6462-6472
·
IF 8.312
Qun Li,Yuantong Tian,Dandi Li,Jianfeng Sun,Donglei Shi,Lin Fang,Yong Gao,Haiyan Liu
A lipid–cisplatin conjugate was synthesized for super-molecular assembly with lipids to form a new generation of liposomal cisplatin formulation, lipocisplatin. In vitro , lipocisplatin has higher efficacy in human ovarian cancer A2780 and human breast cancer MCF-7 with the murine breast cancer cell line 4T1 which is currently an established model for stage IV breast cancer as the most sensitive strain. Moreover, lipocisplatin demonstrated a greater MTD value and relatively longer blood circulation as compared to cisplatin. Lipocisplatin preferentially accumulate drugs to the tumor site, resulting in a better tumor inhibition efficacy. Moreover, lipocisplatin exceeds the size cutoff for kidney clearance, hence it bypasses the nephrotoxicity of cisplatin which is a major curse of one of the most efficient anticancer drugs nowadays in clinic. The results here indicated lipocisplatin may be translated into a new generation of liposomal based cisplatin drug in clinic.
研究领域:
肿瘤学
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药剂学
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纳米医学
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药物递送系统
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癌症治疗
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DOI
高影响因子
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
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2026
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IF 2.4
Meng-Yi Chi,Cong-Ying Zhang,Xiao-Yan Gao,Jia Yu,Chun-Ying Bai,Dan-Dan Hao
The chemotherapeutic agent cisplatin for solid tumors frequently induces cancer-associated cachexia characterized by weight loss and decreased skeletal muscle mass. These adverse cisplatin-related symptoms are dose‑limiting, and the ability to counteract drug-initiated muscle atrophy in cancer-associated cachexia remains a pharmacological challenge. The aim of this study was to determine the protective efficacy of lobetyolin, a natural compound derived from Codonopsis pilosula, known to exert antioxidant, anti‑inflammatory, and anti‑apoptotic activities, against cisplatin-induced skeletal muscle wasting and subsequently elucidate a potential underlying molecular mechanism of action using a mouse model. Mice were injected with cisplatin (4 mg/kg, i.p. every other day, 4 doses in total) with concurrent oral lobetyolin (20 or 40 mg/kg daily) for 8 days. Lobetyolin inhibited cisplatin-induced reductions in body weight and grip strength, ameliorated gastrocnemius muscle atrophy, and preserved myofiber cross‑sectional area. Mechanistically, lobetyolin restored superoxide dismutase (SOD) activity and glutathione (GSH) levels while diminishing malondialdehyde (MDA) content in gastrocnemius muscle. Lobetyolin was found to activate the AKT signaling axis as evidenced by enhanced phosphorylation of AKT (Ser473) and FoxO3α (Thr32), which suppressed FoxO3α nuclear translocation and downregulated the E3 ubiquitin ligase Fbx32, thereby diminishing proteasomal protein degradation. Concurrently, lobetyolin normalized the Bax/Bcl‑2 ratio to inhibit myocyte apoptosis. These findings demonstrated that lobetyolin may be considered as a multi‑targeted therapeutic candidate to counteract oxidative injury, protein catabolism, and myocyte apoptosis initiated by cisplatin. Data suggest that lobetyolin’s potential as a safe adjunctive agent against chemotherapy‑induced muscle wasting might involve AKT/FoxO3α pathway.
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2026
·
IF 8.1
Hanfei Xie,Wumin Dai,Lu Sun,Wangang Gong,Tao Zhu,Yingli Zhang
Ovarian cancer (OV) is a highly lethal gynecological tumor, often developing platinum chemotherapy resistance and treatment failure. With their diverse and complex structures, natural products offer potential solutions to drug resistance. This study systematically examines chaetocin's effects on cisplatin-resistant OV cells and its underlying molecular mechanisms. We utilized a cell counting Kit-8, transwell assays, flow cytometry, immunohistochemistry, and western blotting to evaluate chaetocin's effects on cisplatin-resistant OV cells. Proteomic analysis and bioinformatics were utilized to identify the molecular targets of chaetocin, which were validated via cell transfection and co-immunoprecipitation. Additionally, a cisplatin-resistant OV xenograft model was developed for in vivo studies. Chaetocin suppressed the malignancy of cisplatin-resistant OV cells in a dose-dependent manner to suppress cell proliferation, impede cell migration and invasion, and induce both cell apoptosis and cell cycle arrest. Furthermore, in vivo studies showed that chaetocin inhibited tumor growth in a cisplatin-resistant OV xenograft model. In terms of mechanism, chaetocin induced ferroptosis in these cells, inhibiting TFRC ubiquitination and upregulating its expression by reducing the levels of cullin1 and its neddylation binding (cullin1-NEDD8). Our study uncovers a previously unrecognized mechanism: Chaetocin induces ferroptosis by inhibiting TFRC neddylation to upregulate its expression in OV. Unlike its known role as an SUV39H1 inhibitor, chaetocin functions through the neddylation-TFRC-ferroptosis axis, a pathway not previously linked to this compound. Moreover, while neddylation has recently been reported to regulate ferroptosis via SLC7A11, our study reveals an entirely distinct mechanism involving TFRC-mediated iron transport. This epigenetic regulation stabilizes TFRC, sensitizing resistant cells to ferroptosis, providing a dual-mechanistic insight not found in existing literature. By linking chaetocin's gene regulation to iron-dependent cell death, we offer new insights and potential therapies for cisplatin-resistant OV.
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DOI
高影响因子
Advanced Healthcare Materials
·
2026
·
IF 11
Zi Zhu,Dan Yang,Hao Sun,Nizhaoyue Wei,Zhenkun Fu,Jia Zhang,Zhangdi Yan,Piaoping Yang,He Ding,Lei Zhong
Tumor immunotherapy exerts transformative effects in cancer treatment by leveraging intrinsic immunity and acting broadly effective across cancers, while first-line chemotherapy plays a direct role by disrupting tumor DNA and reducing burden. However, the clinical utility of immunotherapy is notably constrained by the immunosuppressive tumor microenvironment (ITME), while chemotherapy suffers from intrinsic systemic toxicity and acquired resistance. Herein, multifunctional nanozymes on cerium oxide sacrificial templates were designed via precursor engineering, with zirconium introduced to leverage the Kirkendall effect, whereby differing migration rates of zirconium and cerium ions form hierarchical porous structures. Accordingly, such structural features facilitate efficient mass transfer, thereby notably enhancing their triple enzymatic activity. Hierarchical architectures, coupled with hyaluronic acid moieties, further enable high-capacity cisplatin loading and high-specificity tumor targeting, effectively addressing poor drug delivery and off-target issues. Moreover, ultrasound-amplified redox homeostasis modulation driven by the nanozymes’ enzymatic activity acts as a key regulator for disrupting tumor cell redox balance. Meanwhile, synergy between oxidative stress and cisplatin-induced DNA damage acts as a dual stimulus to intervene in tumor survival pathways, not only reversing ITME but also mitigating chemotherapy-associated limitations, thereby fostering concurrent tumor cell death and immunogenic cell death and consequently highlighting promising prospects for malignancy therapy.
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产品关联
DOI
高影响因子
RSC Advances
·
2025
·Vol. 15
·期 22
·17255-17265
·
IF 4.6
Danrui Liu,Wenquan Wang,Yongjun Li,Suai Lin,Qingkun Jiang,Ruiyang Zou,Jiaxuan Qiu
The typically occurring malignant tumor in the head and neck is oral squamous cell carcinoma (OSCC), which is highly aggressive and invasive. Despite surgical advancements, radiation, and chemotherapy, the prognosis for OSCC is still poor. Chemotherapy's effectiveness is frequently restricted by its serious side effects and the development of resistance. In this study, a cisplatin (CDDP)-loaded magnetic targeting nanoplatform (CDDP@PPy@Fe3O4) has been designed for synergistic chemo-photothermal therapy. PPy with carboxyl groups was first prepared by chemical oxidative polymerization. Then, Fe3O4 nanoparticles were synthesized in situ on its surface and loaded with CDDP through a reaction with the carboxyl groups. The CDDP@PPy@Fe3O4 nanocomposite serves not only as a nanocarrier for the targeted delivery of CDDP to alleviate the systemic toxicity of chemotherapy but also possesses excellent photothermal conversion properties, generating localized heat upon near-infrared laser irradiation that enables photothermal therapy. Contrary to using only chemotherapy or photothermal therapy, CDDP@PPy@Fe3O4 nanoparticles combined with NIR exposure exert superior anticancer effects against OSCC both in vivo and in vitro while exhibiting minimal side effects. Therefore, CDDP@PPy@Fe3O4 nanoparticles could be a promising candidate for nanomedicine in OSCC combination therapy.
研究领域:
肿瘤学
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纳米医学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2025
·
IF 3.8
Yue Feng,Ying Zhang,Jinxin Li,Junzhe Yu,Yuan Tian,Zunjian Zhang,Fengguo Xu,Pei Zhang
Cisplatin (DDP) is widely utilized in the clinical treatment of malignant tumors, but its effectiveness is significantly compromised by the adverse effects of acute kidney injury (AKI). Renal tubular cells are primarily responsible for DDP-induced AKI (DDP-AKI); however, the responses of heterogeneous renal tubular cells to DDP exposure have not been thoroughly explored. In this study, we employed a targeted metabolomics approach to investigate the metabolic responses of renal tubular cells in DDP-AKI rats. Tubular cells were isolated from the renal cortex and outer medulla, and a chemical derivatization-based liquid chromatography–tandem mass spectrometry (LC–MS/MS) metabolomics method was applied. Our findings revealed distinct metabolic profiles in tubular cells from the renal cortex and outer medulla, with outer medullary cells exhibiting greater sensitivity to DDP exposure. Further analyses identified the tryptophan pathway as a critical factor contributing to these regional differences. Additional functional investigations showed that intermediate metabolites of the tryptophan pathway alleviated DDP cytotoxicity in both cortical and outer medullary tubular cells primarily through modulation of the Bcl2/Bax and Caspase-3 pathway. This study enhances our understanding of the metabolic characteristics of tubular cells across heterogeneous renal regions in DDP-AKI and facilitates further exploration of the underlying mechanisms of DDP-induced nephrotoxicity.
研究领域:
药理学
·
肾病学
·
代谢组学
·
毒理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Haibin Lu,Weifang Tong,Meixu Jiang,Huimin Liu,Chen Meng,Kai Wang,Xupeng Mu
How to address the resistance of cisplatin (CDDP) has always been a clinical challenge. The resistance mechanism of platinum-based drugs is very complex, including nuclear DNA damage repair, apoptosis escape, and tumor metabolism reprogramming. Tumor cells can switch between mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis and develop resistance to chemotherapy drugs through metabolic variability. In addition, due to the lack of histone protection and a relatively weak damage repair ability, mitochondrial DNA (mtDNA) is more susceptible to damage, which in turn affects mitochondrial OXPHOS and can become a potential target for platinum-based drugs. Therefore, mitochondria, as targets of anticancer drugs, have become a hot topic in tumor resistance research. This study constructed a self-assembled nanotargeted drug delivery system LND-SS-Pt-TPP/HA-CD. β-Cyclodextrin-grafted hydronic acid (HA-CD)-encapsulated prodrug nanoparticles can target CD44 on the tumor surface and further deliver the prodrug to intracellular mitochondria through a triphenylphosphine group (TPP+). Disulfide bonds can be selectively degraded by glutathione (GSH) in mitochondria, releasing lonidamine (LND) and the cisplatin prodrug (Pt(IV)). Under the action of GSH and ascorbic acid, Pt(IV) is further reduced to cisplatin (Pt(II)). Cisplatin can cause mtDNA damage, induce mitochondrial dysfunction and mitophagy, and then affect mitochondrial OXPHOS. Meanwhile, LND can reduce the hexokinase II (HK II) level, induce destruction of mitochondria, and block energy supply by glycolysis inhibition. Ultimately, this self-assembled nano targeted delivery system can synergistically kill cisplatin-resistant lung cancer cells, which supplies an overcome cisplatin resistance choice via the disrupt mitochondria therapy.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）