Cell death mechanisms induced by gold nano-immunoconjugates-mediated photodynamic therapy against human oesophageal cancer stem cells.

IF 5.9 2区医学 Q1 IMMUNOLOGY

Frontiers in Immunology Pub Date : 2025-09-16 eCollection Date: 2025-01-01 DOI:10.3389/fimmu.2025.1585251

Onyisi Christiana Didamson, Rahul Chandran, Heidi Abrahamse

{"title":"Cell death mechanisms induced by gold nano-immunoconjugates-mediated photodynamic therapy against human oesophageal cancer stem cells.","authors":"Onyisi Christiana Didamson, Rahul Chandran, Heidi Abrahamse","doi":"10.3389/fimmu.2025.1585251","DOIUrl":null,"url":null,"abstract":"Background: The current conventional therapy for oesophageal cancer is unable to effectively eliminate oesophageal cancer cells as a result of cancer stem cells (CSCs). These CSCs are the main factors responsible for treatment failure and tumour relapse associated with the present conventional oesophageal cancer therapy. A nano-immunoconjugate-based photodynamic therapy (PDT) proposes a potential approach to eliminate these CSCs efficiently.Method: In this study, we examined the mode of cell death action induced by the nano-immunoconjugates (NIC) mediated PDT comprising aluminium phthalocyanine tetra sulfonic acid chloride (AlPcS4Cl), gold nanoparticles (AuNPs), and anti-CD271 antibody (AlPcS4Cl-AuNPs-anti-CD271) against human oesophageal CSCs in vitro. The oesophageal CSCs were treated with NIC-mediated PDT, and their impacts on cell viability, oxidative stress, mitochondrial membrane, efflux of cytochrome c protein, caspase 3/7 activity, and cell death mechanism were examined. We further evaluated the effects of the treatment on the various phases of the cell cycle, DNA damage response pathways, and autophagy.Results: Findings from this study showed that NIC-mediated PDT significantly inhibited the cell growth of oesophageal CSCs, promoted reactive oxygen species (ROS) production and mitochondrial-mediated apoptotic cell death through the alteration of mitochondrial membrane potential Δψm, high efflux of cytochrome c protein, high activity of caspase 3/7 protease, and early apoptosis. Moreover, NIC-mediated PDT triggered cell cycle checkpoint activity in the G0/G1 phase, stimulated DNA damage response by increased DNA double-strand breaks (DSB) and ATM (ataxia-telangiectasia mutated) upregulation, and activated an autophagy action.Conclusion: The outcomes from this study showed the anticancer efficiency of gold nano-immunoconjugate-based PDT against human oesophageal CSCs. Overall, this study provides a rationale for gold nano-immunoconjugate-based PDT for a promising therapeutic application in the clinical treatment of oesophageal cancer.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1585251"},"PeriodicalIF":5.9000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479469/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fimmu.2025.1585251","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: The current conventional therapy for oesophageal cancer is unable to effectively eliminate oesophageal cancer cells as a result of cancer stem cells (CSCs). These CSCs are the main factors responsible for treatment failure and tumour relapse associated with the present conventional oesophageal cancer therapy. A nano-immunoconjugate-based photodynamic therapy (PDT) proposes a potential approach to eliminate these CSCs efficiently.

Method: In this study, we examined the mode of cell death action induced by the nano-immunoconjugates (NIC) mediated PDT comprising aluminium phthalocyanine tetra sulfonic acid chloride (AlPcS₄Cl), gold nanoparticles (AuNPs), and anti-CD271 antibody (AlPcS₄Cl-AuNPs-anti-CD271) against human oesophageal CSCs in vitro. The oesophageal CSCs were treated with NIC-mediated PDT, and their impacts on cell viability, oxidative stress, mitochondrial membrane, efflux of cytochrome c protein, caspase 3/7 activity, and cell death mechanism were examined. We further evaluated the effects of the treatment on the various phases of the cell cycle, DNA damage response pathways, and autophagy.

Results: Findings from this study showed that NIC-mediated PDT significantly inhibited the cell growth of oesophageal CSCs, promoted reactive oxygen species (ROS) production and mitochondrial-mediated apoptotic cell death through the alteration of mitochondrial membrane potential Δψm, high efflux of cytochrome c protein, high activity of caspase 3/7 protease, and early apoptosis. Moreover, NIC-mediated PDT triggered cell cycle checkpoint activity in the G0/G1 phase, stimulated DNA damage response by increased DNA double-strand breaks (DSB) and ATM (ataxia-telangiectasia mutated) upregulation, and activated an autophagy action.

Conclusion: The outcomes from this study showed the anticancer efficiency of gold nano-immunoconjugate-based PDT against human oesophageal CSCs. Overall, this study provides a rationale for gold nano-immunoconjugate-based PDT for a promising therapeutic application in the clinical treatment of oesophageal cancer.

查看原文本刊更多论文

金纳米免疫偶联物介导的光动力治疗人食管癌干细胞诱导的细胞死亡机制。

背景：由于肿瘤干细胞（cancer stem cells, CSCs）的存在，目前食管癌的常规治疗无法有效消除食管癌细胞。这些CSCs是目前传统食管癌治疗失败和肿瘤复发的主要原因。基于纳米免疫偶联物的光动力疗法（PDT）提出了一种有效消除这些CSCs的潜在方法。方法：采用纳米免疫偶联物（NIC）介导的酞菁四磺酸氯化铝（AlPcS4Cl）、金纳米颗粒（AuNPs）和抗cd271抗体（AlPcS4Cl-AuNPs-anti-CD271）对体外人食管CSCs的PDT诱导细胞死亡模式。采用nici介导的PDT处理食管CSCs，观察其对细胞活力、氧化应激、线粒体膜、细胞色素c蛋白外排、caspase 3/7活性及细胞死亡机制的影响。我们进一步评估了治疗对细胞周期各个阶段、DNA损伤反应途径和自噬的影响。结果：本研究发现，nici介导的PDT通过改变线粒体膜电位Δψm、高细胞色素c蛋白外排、高caspase 3/7蛋白酶活性和早期凋亡，显著抑制食管CSCs的细胞生长，促进活性氧（ROS）的产生和线粒体介导的凋亡细胞死亡。此外，nic介导的PDT在G0/G1期触发细胞周期检查点活性，通过增加DNA双链断裂（DSB）和ATM（共济失调-毛细血管扩张突变）上调刺激DNA损伤反应，并激活自噬作用。结论：基于金纳米免疫偶联物的PDT对人食管CSCs具有一定的抗癌作用。总之，本研究为基于金纳米免疫偶联物的PDT在食管癌临床治疗中的应用提供了理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Frontiers in Immunology IMMUNOLOGY-

CiteScore

9.80

自引率

11.00%

发文量

7153

审稿时长

14 weeks

期刊介绍： Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.