{"title":"靶向正电子发射断层扫描跟踪生物仿生重塑递送可协同增强铁凋亡和火凋亡,从而诱导肺癌消退并提高抗 PD-L1 免疫疗法的疗效","authors":"Jinyu Zhu, Wenyuan Zhou, Yuan Yao, Xin Zhou, Xiaokun Ma, Baohui Zhang, Zhi Yang, Bufu Tang*, Hua Zhu* and Nan Li*, ","doi":"10.1021/acsnano.4c1127810.1021/acsnano.4c11278","DOIUrl":null,"url":null,"abstract":"<p >The chemoresistance and systemic toxicity of cisplatin (CDDP) severely limit its application in the treatment of non-small cell lung cancer (NSCLC). Here, I-124 labeled cancer cell membrane biomimetic nanovesicles loading Polyphyllin VI (PPVI) and CDDP (termed <sup>124</sup>I–P/C@CMLvs) were constructed to enhance the sensitivity and efficacy of CDDP. The radiochemical purity (RCP) of <sup>124</sup>I–P/C@CMLvs reached more than 99% and maintained reliable stability in vitro. Micro-positron emission tomography (micro-PET) imaging of I-124 quantitatively revealed the distribution and specific homologous tumor targeting ability of <sup>124</sup>I–P/C@CMLvs in vivo with superior diagnosis performance, beneficial for dynamically monitoring the efficacy against NSCLC. Loaded PPVI significantly strengthened the sensitivity of NSCLC to CDDP therapy and exerted synergistic anti-tumor effect in vitro and in vivo, which was achieved by PPVI promoting p53 deubiquitination and stimulating reactive oxygen species (ROS) production to trigger the crosstalk between the amplification of GPX4 signaling-mediated ferroptosis and NLRP3/GSDMD/Caspase-1 axis-mediated pyroptosis. <sup>124</sup>I–P/C@CMLvs also significantly stimulated the infiltration of immune cells including dendritic cells, CD8<sup>+</sup> T cells, and CD4<sup>+</sup> T cells in tumor tissues (<i>P</i> < 0.05). The combination of <sup>124</sup>I–P/C@CMLvs and anti-PD-L1 therapy further synergistically promoted NSCLC regression. Altogether, <sup>124</sup>I–P/C@CMLvs provide a transformational solution to the challenge of improving CDDP sensitivity and realizing the integration of diagnosis, treatment, and monitoring of NSCLC.</p>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"18 45","pages":"31401–31420 31401–31420"},"PeriodicalIF":15.8000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Targeted Positron Emission Tomography-Tracked Biomimetic Codelivery Synergistically Amplifies Ferroptosis and Pyroptosis for Inducing Lung Cancer Regression and Anti-PD-L1 Immunotherapy Efficacy\",\"authors\":\"Jinyu Zhu, Wenyuan Zhou, Yuan Yao, Xin Zhou, Xiaokun Ma, Baohui Zhang, Zhi Yang, Bufu Tang*, Hua Zhu* and Nan Li*, \",\"doi\":\"10.1021/acsnano.4c1127810.1021/acsnano.4c11278\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The chemoresistance and systemic toxicity of cisplatin (CDDP) severely limit its application in the treatment of non-small cell lung cancer (NSCLC). Here, I-124 labeled cancer cell membrane biomimetic nanovesicles loading Polyphyllin VI (PPVI) and CDDP (termed <sup>124</sup>I–P/C@CMLvs) were constructed to enhance the sensitivity and efficacy of CDDP. The radiochemical purity (RCP) of <sup>124</sup>I–P/C@CMLvs reached more than 99% and maintained reliable stability in vitro. Micro-positron emission tomography (micro-PET) imaging of I-124 quantitatively revealed the distribution and specific homologous tumor targeting ability of <sup>124</sup>I–P/C@CMLvs in vivo with superior diagnosis performance, beneficial for dynamically monitoring the efficacy against NSCLC. Loaded PPVI significantly strengthened the sensitivity of NSCLC to CDDP therapy and exerted synergistic anti-tumor effect in vitro and in vivo, which was achieved by PPVI promoting p53 deubiquitination and stimulating reactive oxygen species (ROS) production to trigger the crosstalk between the amplification of GPX4 signaling-mediated ferroptosis and NLRP3/GSDMD/Caspase-1 axis-mediated pyroptosis. <sup>124</sup>I–P/C@CMLvs also significantly stimulated the infiltration of immune cells including dendritic cells, CD8<sup>+</sup> T cells, and CD4<sup>+</sup> T cells in tumor tissues (<i>P</i> < 0.05). The combination of <sup>124</sup>I–P/C@CMLvs and anti-PD-L1 therapy further synergistically promoted NSCLC regression. Altogether, <sup>124</sup>I–P/C@CMLvs provide a transformational solution to the challenge of improving CDDP sensitivity and realizing the integration of diagnosis, treatment, and monitoring of NSCLC.</p>\",\"PeriodicalId\":21,\"journal\":{\"name\":\"ACS Nano\",\"volume\":\"18 45\",\"pages\":\"31401–31420 31401–31420\"},\"PeriodicalIF\":15.8000,\"publicationDate\":\"2024-10-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Nano\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acsnano.4c11278\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Nano","FirstCategoryId":"88","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsnano.4c11278","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
摘要
顺铂(CDDP)的化疗耐药性和全身毒性严重限制了它在非小细胞肺癌(NSCLC)治疗中的应用。为提高CDDP的灵敏度和疗效,本文构建了装载聚卟啉Ⅵ(PPVI)和CDDP的I-124标记癌细胞膜仿生纳米颗粒(称为124I-P/C@CMLvs)。124I-P/C@CMLvs 的放射化学纯度(RCP)达到 99% 以上,并在体外保持可靠的稳定性。I-124的显微正电子发射断层成像(micro-PET)定量显示了124I-P/C@CMLvs在体内的分布和特异性同源肿瘤靶向能力,诊断性能优越,有利于动态监测对NSCLC的疗效。负载的PPVI能显著增强NSCLC对CDDP治疗的敏感性,并在体外和体内发挥协同抗肿瘤效应,这是通过PPVI促进p53去泛素化和刺激活性氧(ROS)产生,引发GPX4信号介导的铁变态反应和NLRP3/GSDMD/Caspase-1轴介导的热变态反应之间的串联作用实现的。124I-P/C@CMLvs 还能显著刺激树突状细胞、CD8+ T 细胞和 CD4+ T 细胞等免疫细胞在肿瘤组织中的浸润(P < 0.05)。124I-P/C@CMLvs与抗PD-L1疗法的联合应用进一步协同促进了NSCLC的消退。总之,124I-P/C@CMLvs为提高CDDP的敏感性,实现NSCLC的诊断、治疗和监测一体化提供了一种变革性的解决方案。
Targeted Positron Emission Tomography-Tracked Biomimetic Codelivery Synergistically Amplifies Ferroptosis and Pyroptosis for Inducing Lung Cancer Regression and Anti-PD-L1 Immunotherapy Efficacy
The chemoresistance and systemic toxicity of cisplatin (CDDP) severely limit its application in the treatment of non-small cell lung cancer (NSCLC). Here, I-124 labeled cancer cell membrane biomimetic nanovesicles loading Polyphyllin VI (PPVI) and CDDP (termed 124I–P/C@CMLvs) were constructed to enhance the sensitivity and efficacy of CDDP. The radiochemical purity (RCP) of 124I–P/C@CMLvs reached more than 99% and maintained reliable stability in vitro. Micro-positron emission tomography (micro-PET) imaging of I-124 quantitatively revealed the distribution and specific homologous tumor targeting ability of 124I–P/C@CMLvs in vivo with superior diagnosis performance, beneficial for dynamically monitoring the efficacy against NSCLC. Loaded PPVI significantly strengthened the sensitivity of NSCLC to CDDP therapy and exerted synergistic anti-tumor effect in vitro and in vivo, which was achieved by PPVI promoting p53 deubiquitination and stimulating reactive oxygen species (ROS) production to trigger the crosstalk between the amplification of GPX4 signaling-mediated ferroptosis and NLRP3/GSDMD/Caspase-1 axis-mediated pyroptosis. 124I–P/C@CMLvs also significantly stimulated the infiltration of immune cells including dendritic cells, CD8+ T cells, and CD4+ T cells in tumor tissues (P < 0.05). The combination of 124I–P/C@CMLvs and anti-PD-L1 therapy further synergistically promoted NSCLC regression. Altogether, 124I–P/C@CMLvs provide a transformational solution to the challenge of improving CDDP sensitivity and realizing the integration of diagnosis, treatment, and monitoring of NSCLC.
期刊介绍:
ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.