CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
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2022
·Vol. 100
·期 7
·
IF 2.245
Yanzhen Han,Yan Zhou,Liyuan Zhou,Xiaoyan Jia,Xiangjun Yu,Xiaohong An,Zhe Shi
Chemotherapy is one of the most important strategies in the treatment of cancer; however, chemoresistance restricts the effect of chemotherapy. Growing reports suggest that chloride channel-3 (ClC-3) is involved in regulating the sensitivity of multiple chemotherapeutic agents in the chemotherapy of various tumours, while its role in the chemotherapy of cholangiocarcinoma (CCA) is still poorly understood. Herein, we observed that ClC-3 was highly expressed in CCA chemoresistant tissues and CCA cisplatin-resistant cells QBC939/DDP, and the sensitivities of QBC939 and QBC939/DDP cells to cisplatin were all increased after inhibition of ClC-3. Further mechanism exploration revealed that ClC-3 knockdown reduced the level of autophagy. Furthermore, in both QBC939 and QBC939/DDP cells, the autophagy agonist rapamycin eliminated the increased cisplatin sensitivity of ClC-3 knockdown without affecting ClC-3 expression. Collectively, all the findings demonstrate that ClC-3 knockdown increases cisplatin-induced cell death in CCA cells though inhibiting autophagy, regardless of the occurrence of cisplatin resistance. In addition, our results also suggest that targeted inhibition of ClC-3 may be a potential strategy for chemosensitization in CCA chemotherapy.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2017
·
IF 2.31
Zhi Li,Junya Zhang,Xiaonan Guo,Xinhong Guo,Zhenzhong Zhang
Because of the complications and mutability of cancers, combination of chemotherapy and other therapy with multi-mechanisms would be a bright future for the treatment of cancer. Thus, development of multi-functional tumor-targeted drug delivery systems with two or more than two functions should be of great significance. In the study, the Fe3O4@C nanoparticles linked with thermoresponsive copolymer (MTC-NPs) were synthesized, after that, the magnetic properties and photothermal effects of MTC NPs were evaluated. Compared to the pure water, MTC-NPs absorbed more energy and transform it into heat under the 808 nm laser irradiation, and the temperature could increase over 60℃. In addition, the grafted copolymer with coil-to-globule transition acts as a gatekeeper for the temperature-controlled release of mitoxantrone molecules. The super paramagnetic behavior of MTC-NPs certified by the hysteresis loop gives a negligible coercivity at room temperature. Both in vitro and in vivo studies confirmed that the synergistic combination of magnetic targeting, drug controlled release, and thermochemotherapy improve the anti-tumor efficacy with lower side effects. This nanoparticle is a great potential drug carrier in anti-tumor drugs, which can improve the effect of hyperthermia, increase target distribution in tumor, and enhance curative effect for tumor while reducing normal tissue toxicity.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
Theranostics
·
2022
·
IF 11.6
Pan He,En Ren,Biaoqi Chen,Hu Chen,Hongwei Cheng,Xing Gao,Xiaoliu Liang,Hao Liu,Jingdong Li,Bo Li,Aizheng Chen,Chengchao Chu,Xiaoyuan Chen,Jingsong Mao,Yang Zhang,Gang Liu
Background: Though lipiodol formulations are major options in transcatheter arterial chemoembolization (TACE) of advanced unresectable hepatocellular carcinoma (HCC) in the clinic, their application is severely limited by insufficient physical stability between the hydrophobic lipiodol and hydrophilic drugs; thus, most chemotherapeutic drugs are quickly released into systemic circulation resulting in poor therapeutic outcomes and serious side effects. Methods : The typical hydrophilic drug doxorubicin hydrochloride (DOX) was prepared as a pure nanomedicine and then stably and homogeneously dispersed in lipiodol (SHIFT&DOX) via slightly ultrasonic dispersion. The drug release profiles of SHIFT&DOX were defined in a decellularized liver model. In vivo therapeutic studies were performed in rat-bearing N1S1 orthotopic HCC models and rabbit-bearing VX2 orthotopic HCC models. Results : SHIFT&DOX features an ultrahigh homogeneous dispersibility over 21 days, which far surpassed typical Lipiodol-DOX formulations in clinical practice (less than 0.5 h). SHIFT&DOX also has excellent sustained drug release behavior to improve the local drug concentration dependence and increase the time dependence, leading to remarkable embolic and chemotherapeutic efficacy, and eminent safety in all of the orthotopic HCC models. Conclusions: The carrier-free hydrophilic drug nanoparticle technology-based lipiodol formulation provides a promising approach to solve the problem of drug dispersion in TACE with the potential for a translational pipeline.
研究领域:
肿瘤学
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药剂学
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介入放射学
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2024
·
IF 3.5
Dai Meifang,Lin Bingqian,Li Hao,Wang Youming,Wu Miaomiao,Wei Yanan,Zeng Wenping,Qu Lili,Cang Chunlei,Wang Xingbing
Despite the implementation of novel therapeutic regimens and extensive research efforts, chemoresistance remains a formidable challenge in the treatment of acute myeloid leukemia (AML). Notably, the involvement of lysosomes in chemoresistance has sparked interest in developing lysosome-targeted therapies to sensitize tumor cells to currently approved chemotherapy or as innovative pharmacological approaches. Moreover, as ion channels on the lysosomal membrane are critical regulators of lysosomal function, they present potential as novel targets for enhancing chemosensitivity. Here, we discovered that the expression of a lysosomal cation channel, namely transient receptor potential mucolipin 1 (TRPML1), was elevated in AML cells. Inhibiting TRPML1 individually does not impact the proliferation and apoptosis of AML cells. Importantly, inhibition of TRPML1 demonstrated the potential to modulate the sensitivity of AML cells to chemotherapeutic agents. Exploration of the underlying mechanisms revealed that suppression of TRPML1 impaired autophagy while concurrently increasing the production of reactive oxygen species (ROS) and ROS-mediated lipid peroxidation (Lipid-ROS) in AML cells. Finally, the knockdown of TRPML1 significantly reduced OCI-AML3 tumor growth following chemotherapy in a mouse model of human leukemia. In summary, targeting TRPML1 represents a promising approach for combination therapy aimed at enhancing chemosensitivity in treating AML.
研究领域:
肿瘤学
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细胞生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
ACS Nano
·
2019
·
IF 13.903
Hao Zhao,Jiabao Xu,Wenjing Huang,Guiting Zhan,Yanbing Zhao,Huabing Chen,Xiangliang Yang
Highly efficient nanoarchitectures are of great interest for achieving precise chemotherapy with minimized adverse side effects in cancer therapy. However, a major challenge remains in exploring a rational approach to synthesize spatiotemporally selective vehicles for precise cancer chemotherapy. Here, we demonstrate a rational design of bifunctional light-activatable platinum nanocomplexes (PtNCs) that produce dually cooperative cancer therapy through spatiotemporally selective thermo-chemotherapy. The Pt4+-coordinated polycarboxylic nanogel is explored as the nanoreactor template, which is exploited to synthesize bifunctional PtNCs consisting of a zero-valent Pt0 core and a surrounding bivalent Pt2+ shell with tunable ratios through a facile and controllable reduction. Without light exposure, chemotherapeutic Pt2+ ions are tightly bound on the surface of PtNCs, efficiently reducing undesirable drug leakage and nonselective damage on normal tissues/cells. Upon light exposure, PtNCs generate much heat via photothermal conversion from the Pt0 core and simultaneously trigger a rapid release of chemotherapeutic Pt2+ ions, thereby leading to the spatiotemporally light-activatable synergistic effect of thermo-chemotherapy. Moreover, PtNCs show enhanced tumor accumulation through the heat-triggered hydrophilicity–hydrophobicity transition upon immediate light exposure after injection, dramatically facilitating in vivo tumor regression through their cooperative anticancer efficiency. This rational design of spatiotemporally activatable nanoparticles provides an insightful tool for precise cancer therapy.
研究领域:
纳米技术
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癌症治疗
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材料科学
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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
Biomaterials Science
·
2021
·Vol. 9
·期 19
·6501-6509
·
IF 6.843
Bo Zhang,Chen-wen Shao,Kang-Min Zhou,Qin Li,Yong-Tao Duan,Yu-Shun Yang,Hai-Liang Zhu
Recently, hypothermal photothermal therapy (HPTT) seemed essential for the future clinical transformation of cancer optical therapies. However, at a lower working temperature, heat shock proteins (HSPs) seriously affect the anti-tumor effect of HPTT. This work reports a reasonable design of a dual-responsive nanoplatform for the synergistic treatment of chemotherapy and HPTT. We adopted a one-step method to wrap indocyanine green (ICG) into imidazole skeleton-8 (ZIF-8) and further loaded it with the chemotherapy drug doxorubicin (DOX). Furthermore, we introduced Hsp-70 siRNA to block the affection of HSPs at an upstream node, thereby avoiding the side effects of traditional heat shock protein inhibitors. The prepared ZIF-8@ICG@DOX@siRNA nanoparticles (ZID-Si NPs) could significantly improve the stability of siRNA to effectively down-regulate the expression of HSP70 protein during the photothermal therapy, thus realizing the pH-controlled and NIR-triggered release of the chemotherapeutical drug DOX. Moreover, tumors were also imaged accurately by ICG wrapped in ZID-Si nanoparticles. After the evaluation of the in vitro and in vivo photothermal effect as well as the anti-tumor activity, we found that the added Hsp-70 siRNA enhanced the synergistic anti-cancer activity of HPTT and chemotherapy. In summary, this work holds great potential in cancer treatment, and suggests better efficacy of synergistic chemo/HPTT than the single-agent therapy.
研究领域:
癌症治疗
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纳米技术
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光热疗法
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化疗
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基因沉默
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-11
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IF 5.228
Guo Shengrong,Lv Li,Shen Yuanyuan,Hu Zhongliang,He Qianjun,Chen Xiaoyuan
Small-molecule chemosensitizers can reverse cancer multidrug resistance (MDR), thus significantly improving the in vitro effect of chemotherapy drugs for MDR cancer cells, however, their in vivo effects are not always very good, because they are difficult to effectively accumulate in tumor and enter the same cancer with chemotherapy drugs after systemic administration due to individual biopharmaceutical properties. To overcome these limitations, here we study a novel nanoparticular pre-chemosensitizer which can be also used as nanocarrier of chemotherapy drugs. We take an ‘all in one’ approach to develop a self-assembled nanoparticle formula of amphiphilic poly(curcumin-dithiodipropionic acid)-b-poly(ethylene glycol)-biotin. The nanoparticle is capable of tumor-targeted delivery, responsive degradation at the intracellular level of glutathione and subsequent intracellular co-release of the chemosensitizer curcumin and the encapsulated chemotherapeutic drug doxorubicin to maximize a synergistic effect of chemosensitization and chemotherapy. We demonstrate that the antitumor efficacy of nanoparticle is much superior to that of doxorubicin in the multidrug resistant MCF-7/ADR xenografted nude mice.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2024
·Vol. 15
·期 7
·1-17
·
IF 8.1
Wang Yuying,Su Kunqi,Wang Chang,Deng Tao,Liu Xiaofeng,Sun Shiqi,Jiang Yang,Zhang Chunfeng,Xing Baocai,Du Xiaojuan
Chemotherapeutic efficacy is seriously impeded by chemoresistance in more than half of hepatocellular carcinoma (HCC) patients. However, the mechanisms involved in chemotherapy-induced upregulation of chemoresistant genes are not fully understood. Here, this study unravels a novel mechanism controlling nuclear acetyl-CoA production to activate the transcription of chemoresistant genes in HCC. NAT10 is upregulated in HCC tissues and its upregulation is correlated with poor prognosis of HCC patients. NAT10 is also upregulated in chemoresistant HCC cells. Targeting NAT10 increases the cytotoxicity of chemotherapy in HCC cells and mouse xenografts. Upon chemotherapy, NAT10 translocates from the nucleolus to the nucleus to activate the transcription of CYP2C9 and PIK3R1 . Additionally, nuclear acetyl-CoA is specifically upregulated by NAT10. Mechanistically, NAT10 binds with ACLY in the nucleus and acetylates ACLY at K468 to counteract the SQSTM1-mediated degradation upon chemotherapy. ACLY K468-Ac specifically accumulates in the nucleus and increases nuclear acetyl-CoA production to activate the transcription of CYP2C9 and PIK3R1 through enhancing H3K27ac. Importantly, K468 is required for nuclear localization of ACLY. Significantly, ACLY K468-Ac is upregulated in HCC tissues, and ablation of ACLY K468-Ac sensitizes HCC cells and mouse xenografts to chemotherapy. Collectively, these findings identify NAT10 as a novel chemoresistant driver and the blockage of NAT10-mediated ACLY K468-Ac possesses the potential to attenuate HCC chemoresistance.
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
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Hua Yan,Jiangtao Dong,Xingkun Luan,Chen Wang,Zhenjun Song,Qi Chen,Jujiang Ma,Xuezhong Du
The construction of nanoplatforms for the multimodal cancer therapy still remains an enormous challenge. Ultrathin porous nitrogen-doped carbon coated stoichiometric copper selenide heterostructures (CuSe/NC) are prepared using a facile and green one-pot hydrothermal method. Interestingly, CuSe/NC itself can achieve both photothermal therapy (PTT) and photocatalytic therapy (PCT) under irradiation of a single near-infrared (NIR) light (808 nm), which is convenient and safe for clinical applications. Importantly, the triple-enhanced NIR light-activated PCT, including O2-independent free radicals, Fenton-like reaction, and glutathione (GSH) depletion, breaks through the limitations of hypoxia and overexpressed GSH in cancer cells. Furthermore, CuSe/NC is loaded with doxorubicin (DOX) via metal coordination and then decorates with DNA to construct the CuSe/NC-DOX-DNA nanoplatform. Surprisingly, the facile nanoplatform has an advanced biocomputing capability of an “AND” Boolean logic gate with the smart “AND” logic controlled release of DOX upon combined stimuli of pH and GSH for precise cancer chemotherapy. The synergistic mechanism of proton-mediated ligand exchange between DOX and GSH is proposed for the “AND” logic controlled drug release from CuSe/NC-DOX-DNA. In vitro and in vivo studies demonstrate that CuSe/NC-DOX-DNA has excellent anticancer efficacy and negligible toxicity. This innovative nanoplatform with multienhanced anticancer efficacy provides a paradigm for combination cancer therapy of PTT, PCT, and chemotherapy.
研究领域:
肿瘤学
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纳米医学
·
生物材料学
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DOI
PubMed
高影响因子
Human Cell
·
2025
·Vol. 39
·期 1
·27
·
IF 3.1
Xu Jianfeng,Lei Deng,Xu Peng,Wang Yuqi,Li Zhupeng,Wu Jiacheng,Feng Weizhong,Zhou Junqing
Esophageal cancer (EC) remains a highly aggressive malignancy with limited therapeutic success, partly due to heterogeneous responses to neoadjuvant chemotherapy (NAC). Tumor-derived exosomes and tumor-associated macrophages play critical roles in shaping the immunosuppressive tumor microenvironment, but their crosstalk in EC chemoresistance remains unclear. In this study, we identified tumor-derived exosomal miR-145-5p as a potential predictor of poor NAC response. Elevated exosomal miR-145-5p levels were associated with increased M2 macrophage infiltration and enhanced expression of M2 markers in EC tissues. Mechanistically, miR-145-5p promoted M2 macrophage polarization through the suppression of transferrin receptor (TFRC) and subsequent disruption of iron uptake. Consequently, these tumor-promoting M2-polarized macrophages enhanced EC cell proliferation, migration, invasion, and cisplatin resistance. In vivo, macrophages overexpressing miR-145-5p facilitated tumor growth and markedly weakened the therapeutic effects of cisplatin. Overall, our findings reveal that EC cells utilize exosomal miR-145-5p to remodel macrophages into a pro-tumorigenic phenotype through TFRC-dependent iron metabolic reprogramming, contributing to malignant progression and chemoresistance. Exosomal miR-145-5p may represent a promising biomarker for NAC response and a therapeutic target to improve treatment outcomes in EC.
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Yisheng Peng,Hui Liu,Xiaoliu Liang,Lei Cao,Minglei Teng,Hu Chen,Zhenjie Li,Xuqi Peng,Jingsong Mao,Hongwei Cheng,Gang Liu
Hydrogel, as a promising embolic material for hepatocellular carcinoma (HCC), may fully embolize both major vessels and peripheral microvessels. A self-assembling hydrogel composed of chemotherapeutic drugs offers significant clinical benefits without carrier introduction. Herein, we developed a sustained drug-releasing complex hydrogel (RKT@gel), which was fabricated by the self-assembly of raltitrexed chemotherapeutic drugs (R@gel), along with the incorporation of kaempferol and tantalum nanoparticles (Ta NPs). Kaempferol enhances the mechanical strength of R@gel and inhibits hypoxia-induced angiogenesis post-embolization, improving embolization effectiveness. In addition to enabling X-ray-guided transarterial chemoembolization (TACE), Ta NPs enhance radiation sensitivity. These synergistic effects of RKT@gel not only significantly induce immunogenic cell death, thereby enhancing the activation of dendritic cells, but also activate major histocompatibility complex class I (MHC-I)-mediated antitumor immune recognition and cytotoxicity. In vivo , RKT@gel achieves enhanced tumor deposition and sustained drug release, effectively suppressing tumor progression. Additionally, when combined with radiotherapy, RKT@gel achieves efficient antitumor immunoactivation. Overall, this versatile composite hydrogel not only achieves effective embolization therapy but also substantially triggers antitumor immune responses with good biocompatibility. This multifunctional design provides a TACE-based multidisciplinary strategy for HCC.
研究领域:
肿瘤学
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生物医学工程
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Ruxuan Ma,Liuting Zheng,Han Yu,Da Huo,Huiyue Zhao,Hao Zhang
In recent years, the chiral biological effects of nanomedicines have garnered significant interest. Research has focused on understanding how material chirality affects cellular transcription and metabolism. Stress granules, which are membraneless organelles formed through liquid–liquid phase separation of G3BP1 proteins and related compartments, have been extensively studied and are closely associated with cellular damage repair and metabolism. The role and mechanism of chiral nanomaterials in modulating stress granules remain unclear. This study aimed to investigate the expression and structural characteristics of stress granules under the influence of chiral nanomaterials, both individually and in combination with chemotherapy. A library of chiral ligand-modified materials was constructed, and techniques such as immunofluorescence, live-cell imaging, fluorescence recovery after photobleaching assays, and proximity labeling combined with proteomics analysis were employed. These methods helped identify the protein corona adsorbed on the surface of the nanomaterials and explore their relationship with nanomaterial chirality. The findings suggest that the assembly of stress granules is influenced by chirality and can be regulated by chiral nanomaterials. Additionally, chemotherapy sensitivity in cancer cells was enhanced, and normal cells were protected by leveraging the chiral-dependent modulation of material assembly in stress granules. This study offers insights into the regulation of membraneless cellular structures based on chiral biological effects.
研究领域:
生物物理
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分子生物学
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癌症研究
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材料科学
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细胞生物学
✓ 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）