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

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.