Full Text:   <1860>

Summary:  <15>

Suppl. Mater.: 

CLC number: 

On-line Access: 2025-12-31

Received: 2024-03-25

Revision Accepted: 2024-12-26

Crosschecked: 2025-12-31

Cited: 0

Clicked: 1762

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Chenguang LIU

https://orcid.org/0000-0001-5999-8870

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2025 Vol.26 No.12 P.1260-1268

http://doi.org/10.1631/jzus.B2400163


Drug-assisted synthesis of copper nanoparticles and their induction of cuproptosis and necrosis for breast cancer therapy


Author(s):  Yuewen WANG, Jingjie GAO, Yuying CHENG, Hanling PAN, Hanxiao TANG, Chenguang LIU

Affiliation(s):  Zhejiang Provincial Engineering Research Center of New Technologies and Applications for Targeted Therapy of Major Diseases, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China; more

Corresponding email(s):   cgliu@zstu.edu.cn

Key Words:  Carrier-free nanoparticles, Copper nanoparticles, Cuproptosis, Neurokinin-1 receptor, Aprepitant


Share this article to: More <<< Previous Article|

Yuewen WANG, Jingjie GAO, Yuying CHENG, Hanling PAN, Hanxiao TANG, Chenguang LIU. Drug-assisted synthesis of copper nanoparticles and their induction of cuproptosis and necrosis for breast cancer therapy[J]. Journal of Zhejiang University Science B, 2025, 26(12): 1260-1268.

@article{title="Drug-assisted synthesis of copper nanoparticles and their induction of cuproptosis and necrosis for breast cancer therapy",
author="Yuewen WANG, Jingjie GAO, Yuying CHENG, Hanling PAN, Hanxiao TANG, Chenguang LIU",
journal="Journal of Zhejiang University Science B",
volume="26",
number="12",
pages="1260-1268",
year="2025",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2400163"
}

%0 Journal Article
%T Drug-assisted synthesis of copper nanoparticles and their induction of cuproptosis and necrosis for breast cancer therapy
%A Yuewen WANG
%A Jingjie GAO
%A Yuying CHENG
%A Hanling PAN
%A Hanxiao TANG
%A Chenguang LIU
%J Journal of Zhejiang University SCIENCE B
%V 26
%N 12
%P 1260-1268
%@ 1673-1581
%D 2025
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2400163

TY - JOUR
T1 - Drug-assisted synthesis of copper nanoparticles and their induction of cuproptosis and necrosis for breast cancer therapy
A1 - Yuewen WANG
A1 - Jingjie GAO
A1 - Yuying CHENG
A1 - Hanling PAN
A1 - Hanxiao TANG
A1 - Chenguang LIU
J0 - Journal of Zhejiang University Science B
VL - 26
IS - 12
SP - 1260
EP - 1268
%@ 1673-1581
Y1 - 2025
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2400163


Abstract: 
neurokinin-1 receptor (NK1R), a member of the G protein-coupled receptor (GPCR) family, contributes to multiple pathological processes, including pain, chronic inflammation, and cancer (Gutierrez et al., 2019; Robinson et al., 2023). Current reports and our previous work have proven that NK1R is highly expressed in many cancer cells, such as colorectal cancer and leukemia, and that targeted blocking of NK1R can effectively inhibit tumor cell proliferation (Li XQ et al., 2013; Li JY et al., 2016; Ge et al., 2019; Shi et al., 2021). In addition, GPCRs have been found not only in the plasma membrane but also in the membranes of endosomes and lysosomes with endocytosis (Irannejad et al., 2017; Yarwood et al., 2017), which is more pronounced in cancer cells with highly developed lysosomes (Ramirez-Garcia et al., 2019).

药物辅助制备的铜纳米颗粒及其通过诱导细胞铜死亡和坏死的乳腺癌治疗的研究

王跃文1,高晶杰1,程宇莹1,潘含灵1,唐含笑2,刘晨光1
1浙江理工大学生命科学与医药学院,重大疾病靶向治疗新技术和应用浙江省工程研究中心,中国杭州市,310018
2河南中医药大学中医药科学院,中国郑州市,450046
摘要:铜离子在铜死亡中发挥着关键作用,过量的Cu(I)离子不仅可与脂酰化二氢脂酰胺S-乙酰转移酶(DLAT)结合,诱导其寡聚,还能降低铁-硫簇蛋白的稳定性,从而共同引发细胞铜死亡。在高氧化水平的肿瘤微环境中,单质铜纳米颗粒能够被氧化生成Cu(I)离子。因此,本研究以药物阿瑞匹坦作为稳定剂,辅助合成无载体的药物-铜纳米粒子。通过扫描电子显微镜(SEM)、透射电子显微镜(TEM)、X射线衍射谱(XRD)、X射线光电子能谱(XPS)和傅立叶变换红外光谱(FIIR)等表征手段,证实铜-阿瑞匹坦纳米颗粒的顺利制备。激光共聚焦显微镜成像显示,该纳米颗粒通过内吞作用进入细胞溶酶体。在溶酶体酸性环境中,铜-阿瑞匹坦纳米颗粒发生pH响应性降解,释放出药物。此外,通过阿瑞匹坦和铜死亡的双模作用,乳腺癌细胞增殖被显著抑制。综上,本研究提供了一种无载体药物-铜纳米颗粒的制备方法,为实现药物介导和铜死亡介导的协同肿瘤治疗提供了新策略。

关键词:无载体纳米颗粒;铜纳米颗粒;铜死亡;神经激肽1受体(NK1R);阿瑞匹坦

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]BrojatschJ, LimaH, KarAK, et al., 2014. A proteolytic cascade controls lysosome rupture and necrotic cell death mediated by lysosome-destabilizing adjuvants. PLoS ONE, 9(6):e95032.

[2]ChungK, BangJ, ThacharonA, et al., 2022. Non-oxidized bare copper nanoparticles with surface excess electrons in air. Nat Nanotechnol, 17(3):285-291.

[3]GeCT, HuangHM, HuangFY, et al., 2019. Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload. Proc Natl Acad Sci USA, 116(39):19635-19645.

[4]GuanHQ, HarrisC, SunSH, 2023. Metal–ligand interactions and their roles in controlling nanoparticle formation and functions. Acc Chem Res, 56(12):1591-1601.

[5]GutierrezS, Alvarado-VázquezPA, EisenachJC, et al., 2019. Tachykinins modulate nociceptive responsiveness and sensitization: in vivo electrical characterization of primary sensory neurons in tachykinin knockout (Tac1 KO) mice. Mol Pain, 15:1744806919845750.

[6]Gyrd-HansenM, NylandstedJ, JäätteläM, 2004. Heat shock protein 70 promotes cancer cell viability by safeguarding lysosomal integrity. Cell Cycle, 3(12):1484-1485.

[7]HuHL, ZhangWW, LeiL, et al., 2024. Combination losartan with hyaluronic acid modified diethyldithiocarbamate loaded hollow copper sulfide nanoparticles for the treatment of breast cancer and metastasis. Chin Chem Lett, 35(3):108765.

[8]IrannejadR, PessinoV, MikaD, et al., 2017. Functional selectivity of GPCR-directed drug action through location bias. Nat Chem Biol, 13(7):799-806.

[9]JianuOA, LescisinM, WangZ, et al., 2016. X-ray diffraction of crystallization of copper (II) chloride for improved energy utilization in hydrogen production. Int J Hydrogen Energy, 41(19):7848-7853.

[10]KimJY, HongD, LeeJC, et al., 2021. Quasi-graphitic carbon shell-induced Cu confinement promotes electrocatalytic CO2 reduction toward C2+ products. Nat Commun, 12:3765.

[11]KorbelikM, SunJH, CecicI, 2005. Photodynamic therapy–induced cell surface expression and release of heat shock proteins: relevance for tumor response. Cancer Res, 65(3):1018-1026.

[12]LiDY, HaEN, ZhouZL, et al., 2024. “Spark” PtMnIr nanozymes for electrodynamic-boosted multienzymatic tumor immunotherapy. Adv Mater, 36(13):2308747.

[13]LiJY, ZengQ, ZhangYX, et al., 2016. Neurokinin-1 receptor mediated breast cancer cell migration by increased expression of MMP-2 and MMP-14. Eur J Cell Biol, 95(10):368-377.

[14]LiXQ, MaGD, MaQY, et al., 2013. Neurotransmitter substance P mediates pancreatic cancer perineural invasion via NK-1R in cancer cells. Mol Cancer Res, 11(3):294-302.

[15]LinHR, ZhouY, WangJM, et al., 2021. Repurposing ICG enables MR/PA imaging signal amplification and iron depletion for iron-overload disorders. Sci Adv, 7(51):eabl5862.

[16]LiuCG, FuCP, ShiYH, et al., 2022. Dual-responsive nanomotors for deep tumor penetration and subcellular arrangement. Mater Des, 222:111039.

[17]LiuCG, GuoLX, WangY, et al., 2023. Delivering metal ions by nanomaterials: turning metal ions into drug-like cancer theranostic agents. Coord Chem Rev, 494:215332.

[18]NématiF, DubernetC, de VerdièreAC, et al., 1994. Some parameters influencing cytotoxicity of free doxorubicin and doxorubicin-loaded nanoparticles in sensitive and multidrug resistant leucemic murine cells: incubation time, number of nanoparticles per cell. Int J Pharm, 102(1-3):55-62.

[19]NogusaT, CooperCB, YuZA, et al., 2023. Tunable, reusable, and recyclable perfluoropolyether periodic dynamic polymers with high underwater adhesion strength. Matter, 6(7):2439-2453.

[20]NorouziM, YathindranathV, ThliverisJA, et al., 2020. Doxorubicin-loaded iron oxide nanoparticles for glioblastoma therapy: a combinational approach for enhanced delivery of nanoparticles. Sci Rep, 10:11292.

[21]PanYJ, XuPY, ChenBQ, et al., 2020. Supercritical antisolvent process-assisted fabrication of chrysin-polyvinylpyrrolidone sub-microparticles for improved anticancer efficiency. J Supercrit Fluids, 162:104847.

[22]PiWM, WuLY, LuJH, et al., 2023. A metal ions-mediated natural small molecules carrier-free injectable hydrogel achieving laser-mediated photo-fenton-like anticancer therapy by synergy apoptosis/cuproptosis/anti-inflammation. Bioact Mater, 29:98-115.

[23]PlatzmanI, BrenerR, HaickH, et al., 2008. Oxidation of polycrystalline copper thin films at ambient conditions. J Phys Chem C, 112(4):1101-1108.

[24]Ramírez-GarcíaPD, RetamalJS, ShenoyP, et al., 2019. A pH-responsive nanoparticle targets the neurokinin 1 receptor in endosomes to prevent chronic pain. Nat Nanotechnol, 14(12):1150-1159.

[25]RobinsonP, CoveñasR, MuñozM, 2023. Combination therapy of chemotherapy or radiotherapy and the neurokinin-1 receptor antagonist aprepitant: a new antitumor strategy? Curr Med Chem, 30(16):1798-1812.

[26]ShadleCR, MurphyMG, LiuY, et al., 2012. A single-dose bioequivalence and food effect study with aprepitant and fosaprepitant dimeglumine in healthy young adult subjects. Clin Pharmacol Drug Dev, 1(3):93-101.

[27]ShiY, WangX, MengYM, et al., 2021. A novel mechanism of endoplasmic reticulum stress- and c-Myc-degradation-mediated therapeutic benefits of antineurokinin-1 receptor drugs in colorectal cancer. Adv Sci (Weinh), 8(21):e2101936.

[28]SuWQ, XuP, PetzoldR, et al., 2023. Ligand-to-copper charge-transfer-enabled C–H sulfoximination of arenes. Org Lett, 25(6):1025-1029.

[29]SunXQ, GaoXH, WangYY, et al., 2022. Study of the mechanism of nitrogen doping in carbon supports on promoting electrocatalytic oxygen reduction reaction over platinum nanoparticles. J Fuel Chem Technol, 50(11):1427-1436.

[30]TongF, HuHL, XuYY, et al., 2023. Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages. Acta Pharm Sin B, 13(8):3471-3488.

[31]TsvetkovP, CoyS, PetrovaB, et al., 2022. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science, 375(6586):1254-1261.

[32]UpadhyayLSB, KumarN, 2017. Green synthesis of copper nanoparticle using glucose and polyvinylpyrrolidone (PVP). Inorg Nano-Metal Chem, 47(10):1436-1440.

[33]WangYT, ZhouW, JiaRR, et al., 2020. Unveiling the activity origin of a copper-based electrocatalyst for selective nitrate reduction to ammonia. Angew Chem Int Ed, 59(13):5350-5354.

[34]WongKY, NieZY, WongMS, et al., 2024. Metal–drug coordination nanoparticles and hydrogels for enhanced delivery. Adv Mater, 36(26):2404053.

[35]XieJM, YangYN, GaoYB, et al., 2023. Cuproptosis: mechanisms and links with cancers. Mol Cancer, 22:46.

[36]YangLF, YangPP, LipGYH, et al., 2023. Copper homeostasis and cuproptosis in cardiovascular disease therapeutics. Trends Pharmacol Sci, 44(9):573-585.

[37]YangWC, WangYX, HuangYZ, et al., 2023. 4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to promote cuproptosis in colorectal cancer. Biomed Pharmacother, 159:114301.

[38]YarwoodRE, ImlachWL, LieuT, et al., 2017. Endosomal signaling of the receptor for calcitonin gene-related peptide mediates pain transmission. Proc Natl Acad Sci USA, 114(46):12309-12314.

[39]YeoS, AnJ, ParkC, et al., 2020. Design and characterization of phosphatidylcholine-based solid dispersions of aprepitant for enhanced solubility and dissolution. Pharmaceutics, 12(5):407.

[40]YuanDM, LiQ, ZhangQ, et al., 2016. Efficacy and safety of neurokinin-1 receptor antagonists for prevention of chemotherapy-induced nausea and vomiting: systematic review and meta-analysis of randomized controlled trials. Asian Pac J Cancer Prev, 17(4):1661-1675.

[41]ZhangY, ZhouQ, LuL, et al., 2023. Copper induces cognitive impairment in mice via modulation of cuproptosis and CREB signaling. Nutrients, 15(4):972.

[42]ZhengHQ, GaoCB, PengBW, et al., 2011. pH-responsive drug delivery system based on coordination bonding in a mesostructured surfactant/silica hybrid. J Phys Chem C, 115(15):7230-7237.

[43]ZhengHQ, XingL, CaoYY, et al., 2013. Coordination bonding based pH-responsive drug delivery systems. Coordin Chem Rev, 257(11):1933-1944.

[44]ZhouZQ, GongF, ZhangP, et al., 2022. Natural product curcumin-based coordination nanoparticles for treating osteoarthritis via targeting Nrf2 and blocking NLRP3 inflammasome. Nano Res, 15(4):3338-3345.

[45]ZhuY, NiuXG, DingCY, et al., 2024a. Carrier-free self-assembly nano-sonosensitizers for sonodynamic-amplified cuproptosis-ferroptosis in glioblastoma therapy. Adv Sci (Weinh), 11(23):2402516.

[46]ZhuY, NiuXG, WuTT, et al., 2024b. Metal-phenolic nanocatalyst rewires metabolic vulnerability for catalytically amplified ferroptosis. Chem Eng J, 485:150126.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2026 Journal of Zhejiang University-SCIENCE