Zhixin Zhou, Cheng Zhou, Jia Liu, Ye Yuan, Chundong Yao, Miaodeng Liu, Lixue Deng, Jia Sun, Zuoyu Chen, Lin Wang, Zheng Wang
{"title":"用于癌症精准治疗的肿瘤特异性原位合成治疗剂。","authors":"Zhixin Zhou, Cheng Zhou, Jia Liu, Ye Yuan, Chundong Yao, Miaodeng Liu, Lixue Deng, Jia Sun, Zuoyu Chen, Lin Wang, Zheng Wang","doi":"10.1186/s12951-024-02825-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Traditional chemotherapeutic agents suffer from a lack of selectivity, poor targeting ability, and drug resistance. Developing tumor-specific therapies is crucial for precisely eliminating tumors while circumventing toxicity to normal tissues. Disulfiram (DSF), an FDA-approved drug for treating alcohol dependence, exhibits antitumor effect by forming complexes with copper ions (Cu(DDC)<sub>2</sub>). Here, we developed a Cu-doped polydopamine-based nanosystem (DSF@CuPDA-PEGM) to achieve in situ generation of toxic Cu(DDC)<sub>2</sub>.</p><p><strong>Results: </strong>In cancer cells with elevated H<sub>2</sub>O<sub>2</sub> contents, CuPDA responsively degrades to release Cu ions and DSF, allowing on-site synthesis of Cu(DDC)<sub>2</sub> with potent antitumor activity. DSF@CuPDA-PEGM exhibits excellent therapeutic efficacy against both drug-sensitive and drug-resistant cancer cells while minimizing toxicity to noncancerous cells. Moreover, DSF@CuPDA-PEGM promotes the immune response by inducing cancer cell immunogenic death, thereby augmenting anti-PD-1-based immune checkpoint blockade therapy.</p><p><strong>Conclusion: </strong>A tumor-specifically degradable Cu-doped polydopamine-based nanosystem is developed to achieve in situ synthesis of antitumor compounds, providing a promising approach to precisely eliminate tumors and heighten chemo-immunotherapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":null,"pages":null},"PeriodicalIF":10.6000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Tumor specific in situ synthesis of therapeutic agent for precision cancer therapy.\",\"authors\":\"Zhixin Zhou, Cheng Zhou, Jia Liu, Ye Yuan, Chundong Yao, Miaodeng Liu, Lixue Deng, Jia Sun, Zuoyu Chen, Lin Wang, Zheng Wang\",\"doi\":\"10.1186/s12951-024-02825-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Traditional chemotherapeutic agents suffer from a lack of selectivity, poor targeting ability, and drug resistance. Developing tumor-specific therapies is crucial for precisely eliminating tumors while circumventing toxicity to normal tissues. Disulfiram (DSF), an FDA-approved drug for treating alcohol dependence, exhibits antitumor effect by forming complexes with copper ions (Cu(DDC)<sub>2</sub>). Here, we developed a Cu-doped polydopamine-based nanosystem (DSF@CuPDA-PEGM) to achieve in situ generation of toxic Cu(DDC)<sub>2</sub>.</p><p><strong>Results: </strong>In cancer cells with elevated H<sub>2</sub>O<sub>2</sub> contents, CuPDA responsively degrades to release Cu ions and DSF, allowing on-site synthesis of Cu(DDC)<sub>2</sub> with potent antitumor activity. DSF@CuPDA-PEGM exhibits excellent therapeutic efficacy against both drug-sensitive and drug-resistant cancer cells while minimizing toxicity to noncancerous cells. Moreover, DSF@CuPDA-PEGM promotes the immune response by inducing cancer cell immunogenic death, thereby augmenting anti-PD-1-based immune checkpoint blockade therapy.</p><p><strong>Conclusion: </strong>A tumor-specifically degradable Cu-doped polydopamine-based nanosystem is developed to achieve in situ synthesis of antitumor compounds, providing a promising approach to precisely eliminate tumors and heighten chemo-immunotherapy.</p>\",\"PeriodicalId\":16383,\"journal\":{\"name\":\"Journal of Nanobiotechnology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.6000,\"publicationDate\":\"2024-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Nanobiotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1186/s12951-024-02825-6\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nanobiotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1186/s12951-024-02825-6","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:传统化疗药物存在选择性不足、靶向能力差和耐药性等问题。开发肿瘤特异性疗法对于精确消除肿瘤,同时避免对正常组织的毒性至关重要。双硫仑(DSF)是美国 FDA 批准用于治疗酒精依赖症的药物,它通过与铜离子形成络合物(Cu(DDC)2)来发挥抗肿瘤作用。在此,我们开发了一种铜掺杂多巴胺基纳米系统(DSF@CuPDA-PEGM),以实现原位生成有毒的 Cu(DDC)2:结果:在H2O2含量升高的癌细胞中,CuPDA会响应性降解,释放出铜离子和DSF,从而现场合成具有强效抗肿瘤活性的Cu(DDC)2。DSF@CuPDA-PEGM 对药物敏感和耐药的癌细胞都有很好的疗效,同时对非癌细胞的毒性最小。此外,DSF@CuPDA-PEGM 还能通过诱导癌细胞免疫原性死亡来促进免疫反应,从而增强基于抗 PD-1 的免疫检查点阻断疗法:结论:开发了一种肿瘤特异性可降解铜掺杂多巴胺纳米系统,实现了抗肿瘤化合物的原位合成,为精确消除肿瘤和加强化疗免疫疗法提供了一种前景广阔的方法。
Tumor specific in situ synthesis of therapeutic agent for precision cancer therapy.
Background: Traditional chemotherapeutic agents suffer from a lack of selectivity, poor targeting ability, and drug resistance. Developing tumor-specific therapies is crucial for precisely eliminating tumors while circumventing toxicity to normal tissues. Disulfiram (DSF), an FDA-approved drug for treating alcohol dependence, exhibits antitumor effect by forming complexes with copper ions (Cu(DDC)2). Here, we developed a Cu-doped polydopamine-based nanosystem (DSF@CuPDA-PEGM) to achieve in situ generation of toxic Cu(DDC)2.
Results: In cancer cells with elevated H2O2 contents, CuPDA responsively degrades to release Cu ions and DSF, allowing on-site synthesis of Cu(DDC)2 with potent antitumor activity. DSF@CuPDA-PEGM exhibits excellent therapeutic efficacy against both drug-sensitive and drug-resistant cancer cells while minimizing toxicity to noncancerous cells. Moreover, DSF@CuPDA-PEGM promotes the immune response by inducing cancer cell immunogenic death, thereby augmenting anti-PD-1-based immune checkpoint blockade therapy.
Conclusion: A tumor-specifically degradable Cu-doped polydopamine-based nanosystem is developed to achieve in situ synthesis of antitumor compounds, providing a promising approach to precisely eliminate tumors and heighten chemo-immunotherapy.
期刊介绍:
Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.