Xueyu Zhu, Chenyang Bi, Wei Cao, Shuangshuang Li, Chuting Yuan, Pengping Xu, Dongdong Wang, Qianwang Chen and Lei Zhang
{"title":"一种自组装的铜-青蒿素纳米药物,作为治疗癌症的高效活性氧放大级联系统。","authors":"Xueyu Zhu, Chenyang Bi, Wei Cao, Shuangshuang Li, Chuting Yuan, Pengping Xu, Dongdong Wang, Qianwang Chen and Lei Zhang","doi":"10.1039/D4TB01237B","DOIUrl":null,"url":null,"abstract":"<p >Chemodynamic therapy (CDT) is a tumor-specific intervention methodology, which is based on the upregulation of reactive oxygen species (ROS) content by triggering the Fenton or Fenton-like reaction within the tumor microenvironment (TME). However, there are still challenges in achieving high-efficiency CDT on account of both the limited intracellular hydrogen peroxide (H<small><sub>2</sub></small>O<small><sub>2</sub></small>) and delivery efficiency of Fenton metal ions. Copper-based nanotherapeutic systems have attracted extensive attention and have been widely applied in the construction of nanotherapeutic systems and multimodal synergistic therapy. Herein, we propose a strategy to synergize chemotherapy drugs that upregulate intracellular ROS content with chemodynamic therapy and construct an artemisinin-copper nanoprodrug for proof-of-concept. With the proposed biomimetic self-assembly strategy, we successfully construct an injectable nanoprodrug with suitable size distribution and high drug loading content (68.1 wt%) through the self-assembly of amphiphilic artemisinin prodrug and copper ions. After reaching the TME, both Cu<small><sup>2+</sup></small> ions and free AH drugs can be released from AHCu nanoprodrugs. Subsequently, the disassembled Cu<small><sup>2+</sup></small> ions are converted into Cu<small><sup>+</sup></small> ions by consuming the intracellular GSH. The generated Cu<small><sup>+</sup></small> ions serve as a highly efficient Fenton-like reagent for robust ROS generation from both AH and tumor-over-produced H<small><sub>2</sub></small>O<small><sub>2</sub></small>. Results show that the nanoprodrug can realize the cascade amplification of ROS generation <em>via</em> artemisinin delivery and subsequent <em>in situ</em> Fenton-like reaction and a high tumor inhibition rate of 62.48% <em>in vivo</em>. This work provides a promising strategy for the design and development of an efficient nanoprodrug for tumor-specific treatment.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":null,"pages":null},"PeriodicalIF":6.1000,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A self-assembled copper-artemisinin nanoprodrug as an efficient reactive oxygen species amplified cascade system for cancer treatment†\",\"authors\":\"Xueyu Zhu, Chenyang Bi, Wei Cao, Shuangshuang Li, Chuting Yuan, Pengping Xu, Dongdong Wang, Qianwang Chen and Lei Zhang\",\"doi\":\"10.1039/D4TB01237B\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Chemodynamic therapy (CDT) is a tumor-specific intervention methodology, which is based on the upregulation of reactive oxygen species (ROS) content by triggering the Fenton or Fenton-like reaction within the tumor microenvironment (TME). However, there are still challenges in achieving high-efficiency CDT on account of both the limited intracellular hydrogen peroxide (H<small><sub>2</sub></small>O<small><sub>2</sub></small>) and delivery efficiency of Fenton metal ions. Copper-based nanotherapeutic systems have attracted extensive attention and have been widely applied in the construction of nanotherapeutic systems and multimodal synergistic therapy. Herein, we propose a strategy to synergize chemotherapy drugs that upregulate intracellular ROS content with chemodynamic therapy and construct an artemisinin-copper nanoprodrug for proof-of-concept. With the proposed biomimetic self-assembly strategy, we successfully construct an injectable nanoprodrug with suitable size distribution and high drug loading content (68.1 wt%) through the self-assembly of amphiphilic artemisinin prodrug and copper ions. After reaching the TME, both Cu<small><sup>2+</sup></small> ions and free AH drugs can be released from AHCu nanoprodrugs. Subsequently, the disassembled Cu<small><sup>2+</sup></small> ions are converted into Cu<small><sup>+</sup></small> ions by consuming the intracellular GSH. The generated Cu<small><sup>+</sup></small> ions serve as a highly efficient Fenton-like reagent for robust ROS generation from both AH and tumor-over-produced H<small><sub>2</sub></small>O<small><sub>2</sub></small>. Results show that the nanoprodrug can realize the cascade amplification of ROS generation <em>via</em> artemisinin delivery and subsequent <em>in situ</em> Fenton-like reaction and a high tumor inhibition rate of 62.48% <em>in vivo</em>. This work provides a promising strategy for the design and development of an efficient nanoprodrug for tumor-specific treatment.</p>\",\"PeriodicalId\":83,\"journal\":{\"name\":\"Journal of Materials Chemistry B\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-08-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Materials Chemistry B\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2024/tb/d4tb01237b\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Materials Chemistry B","FirstCategoryId":"1","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/tb/d4tb01237b","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
A self-assembled copper-artemisinin nanoprodrug as an efficient reactive oxygen species amplified cascade system for cancer treatment†
Chemodynamic therapy (CDT) is a tumor-specific intervention methodology, which is based on the upregulation of reactive oxygen species (ROS) content by triggering the Fenton or Fenton-like reaction within the tumor microenvironment (TME). However, there are still challenges in achieving high-efficiency CDT on account of both the limited intracellular hydrogen peroxide (H2O2) and delivery efficiency of Fenton metal ions. Copper-based nanotherapeutic systems have attracted extensive attention and have been widely applied in the construction of nanotherapeutic systems and multimodal synergistic therapy. Herein, we propose a strategy to synergize chemotherapy drugs that upregulate intracellular ROS content with chemodynamic therapy and construct an artemisinin-copper nanoprodrug for proof-of-concept. With the proposed biomimetic self-assembly strategy, we successfully construct an injectable nanoprodrug with suitable size distribution and high drug loading content (68.1 wt%) through the self-assembly of amphiphilic artemisinin prodrug and copper ions. After reaching the TME, both Cu2+ ions and free AH drugs can be released from AHCu nanoprodrugs. Subsequently, the disassembled Cu2+ ions are converted into Cu+ ions by consuming the intracellular GSH. The generated Cu+ ions serve as a highly efficient Fenton-like reagent for robust ROS generation from both AH and tumor-over-produced H2O2. Results show that the nanoprodrug can realize the cascade amplification of ROS generation via artemisinin delivery and subsequent in situ Fenton-like reaction and a high tumor inhibition rate of 62.48% in vivo. This work provides a promising strategy for the design and development of an efficient nanoprodrug for tumor-specific treatment.
期刊介绍:
Journal of Materials Chemistry A, B & C cover high quality studies across all fields of materials chemistry. The journals focus on those theoretical or experimental studies that report new understanding, applications, properties and synthesis of materials. Journal of Materials Chemistry A, B & C are separated by the intended application of the material studied. Broadly, applications in energy and sustainability are of interest to Journal of Materials Chemistry A, applications in biology and medicine are of interest to Journal of Materials Chemistry B, and applications in optical, magnetic and electronic devices are of interest to Journal of Materials Chemistry C.Journal of Materials Chemistry B is a Transformative Journal and Plan S compliant. Example topic areas within the scope of Journal of Materials Chemistry B are listed below. This list is neither exhaustive nor exclusive:
Antifouling coatings
Biocompatible materials
Bioelectronics
Bioimaging
Biomimetics
Biomineralisation
Bionics
Biosensors
Diagnostics
Drug delivery
Gene delivery
Immunobiology
Nanomedicine
Regenerative medicine & Tissue engineering
Scaffolds
Soft robotics
Stem cells
Therapeutic devices