An Anti‐inflammatory Fe3O4‐Porphyrin Nanohybrid Capable of Apoptosis through Upregulation of p21 Kinase Inhibitor Having Immunoprotective Properties under Anticancer PDT Conditions. (15th November 2021)

• Record Type: Journal Article
• Authors: Sengupta, Devashish; Das, Subhojit; Sharma, Debdulal; Chattopadhyaya, Saran; Mukherjee, Avinaba; Mazumdar, Zeaul Hoque; Das, Biswajit; Basu, Samita; Sengupta, Mahuya
• Is Part Of: ChemMedChem. Volume 17:Number 2(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-11-15
• Subjects: superparamagnetic Fe3O4-porphyirn nanohybrids -- human gastric (AGS) cell lines -- photodynamic therapy (PDT)-induced apoptosis -- p21 kinase inhibitor -- macrophages -- nitric oxide release and superoxide ions; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202100550
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: We report the influence of Fe3 O4 nanoparticles (NPs) on porphyrins in the development of photosensitizers (PSs) for efficient photodynamic therapy (PDT) and possible post‐PDT responses for inflicting cancer cell death. Except for Au, most metal‐based nanomaterials are unsuitable for clinical applications. The US Food and Drug Administration and other agencies have approved Feraheme and a few other iron oxide NPs for clinical use, paving the way for novel biocompatible immunoprotective superparamagnetic iron oxide nanohybrids to be developed as nanotherapeutics. A water‐soluble nanohybrid, referred to here as E‐NP, comprising superparamagnetic Fe3 O4 NPs functionalised with tripyridyl porphyrin PS was introduced through a rigid 4‐carboxyphenyl linker. As a PDT agent, the efficacy of E‐NP toward the AGS cancer cell line showed enhanced photosensitising ability as determined through in vitro photobiological assays. The cellular uptake of E‐NPs by AGS cells led to apoptosis by upregulating ROS through cell‐cycle arrest and loss of mitochondrial membrane potential. The subcellular localisation of the PSs in mitochondria stimulated apoptosis through upregulation of p21, a proliferation inhibitor capable of preventing tumour development. Under both PDT and non‐PDT conditions, this nanohybrid can act as an anti‐inflammatory agent by decreasing the production of NO and superoxide ions in murine macrophages, thus minimising collateral damage to healthy cells. Abstract : Anticancer PDT agent : Because nanocomposites are mostly considered unsuitable for clinical trials, we propose a biologically active anticancer PDT nanohybrid that could find commercial application. This nanohybrid can promote PDT activity through effective ROS generation. It promotes apoptosis in cancer cells and upregulates p21 kinase by arresting the cell cycle at the G0 ‐G1 stage. The nanohybrid shows concomitant immunoprotective and anti‐inflammatory properties that are apparent through the lowering of both superoxide anion and nitric oxide release in murine macrophages.