An Anti‐inflammatory Fe₃O₄‐Porphyrin Nanohybrid Capable of Apoptosis through Upregulation of p21 Kinase Inhibitor Having Immunoprotective Properties under Anticancer PDT Conditions

Abstract

We report the influence of Fe 3 O 4 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 Fe 3 O 4 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 cellcycle 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 antiinflammatory agent by decreasing the production of NO and superoxide ions in murine macrophages, thus minimising collateral damage to healthy cells.

One-pot synthesis to prepare lignin/photoacid nanohybrids for multifunctional biosensors and photo-triggered singlet oxygen generation

“…The singlet oxygen quantum yield of AL-Por-PP-3 was calculated as 0.62, which is comparable to those of other porphyrin-based materials in the related research studies for singlet oxygen generation and PDT. 43,[86][87][88][89] These results validate that the AL-Por-PP nanoparticles have high photostability and ability to generate singlet oxygen for potential PDT usage.…”

Photodynamic therapy induced cell cycle arrest and cancer cell synchronization: review

“…However, it is shown that 5-aminolaevulinic acid (5-ALA) as a second generation of protoporphyrin IX PSs in PDT has no effect on CC but, as radiosensitizer (for gamma radiation), can stop oral squamous cell carcinoma at G2/M stage ( 136 , 137 ). Furthermore, it is reported by Sengupta and collogues that Fe 3 O 4 nanoparticles (NPs) on porphyrins has immune-protective effects and capable apoptosis via upregulations of p21 kinase by CCA at the G0/G1 stage in AGS and RAW cell lines ( 140 , 142 ). In addition, the results of Radzi and co-workers demonstrated that applying indocyanine green (ICG) and PDT induces G0/G1 arrest and apoptosis in the B16F10 cells; moreover, PDT and hyperthermia had synergistic outcomes in the treatment of B16F10 cells ( 143 ).…”

Porphyrins in Photodynamic Therapy: A Review

“…License: CC BY-NC-ND 4.0 generation PSs, on the other hand, are multifunctional entities with improved tumour targeting capability, generally achieved by conjugation of a PS molecule with antibody conjugates or through nanoencapsulation, or moieties capable of performing therapeutic, diagnostic as well as targeting functions. 35,[86][87][88][89][90][91][92][93][94][95][96][97][98] Ideal PSs are molecules that can be activated by specific wavelengths of light, typically in the visible or near-infrared range, to produce reactive oxygen species (ROS) that can destroy target cells or tissues. The characteristics of an ideal PS can vary depending on the specific application, but generally, it should possess the following attributes:…”