An Anti-inflammatory Fe3 O4 -Porphyrin Nanohybrid Capable of Apoptosis through Upregulation of p21 Kinase Inhibitor Having Immunoprotective Properties under Anticancer PDT Conditions.

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.

meso-Thiophenium Porphyrins and Their Zn(II) Complexes: A New Category of Cationic Photosensitizers.

A new category of cationic meso-thiophenium porphyrins are introduced as possible alternatives to the popular meso-pyridinium porphyrins. Combinations of cationic porphyrins bearing meso-2-methylthiophenium and meso-4-hydroxyphenyl moieties T2(OH)2M (A2B2 type) and T(OH)3M (AB3 type) along with their zinc(II) complexes T2(OH)2MZn and T(OH)3MZn, are reported. The increase in the number of thienyl groups attached to the meso-positions of the porphyrin derivatives (A2B2 frame) has been shown to impart longer fluorescence lifetimes and stronger photocytotoxicity toward A549 lung cancer cells, as evident with T2(OH)2M and its corresponding diamagnetic metal complex T2(OH)2MZn. The photoactivated T2(OH)2MZn imparts an early stage reactive oxygen species (ROS) upregulation and antioxidant depletion in A549 cells and contributes to the strongest oxidative stress-induced cell death mechanism in the series. The DFT calculations of the singlet-triplet energy gap (ΔE) of all the four hydrophilic thiophenium porphyrin derivatives establish the potential applicability of these cationic photosensitizers as PDT agents.

Benzamide porphyrins with directly conjugated and distal pyridyl or pyridinium groups substituted to the porphyrin macrocycles: Study of the photosensitising abilities as inducers of apoptosis in cancer cells under photodynamic conditions.

Amphiphilic porphyrin photosensitisers (PSs) having combinations of directly substituted pyridyl group(s) at the meso-position of a porphyrin macrocycle, and/or indirectly linked pyridyl groups as benzamide derivatives are reported. The compounds 5,10,15,20-tetrakis-(4-pyridylbenzamide)porphyrin (A.2), 5,10,15,20-tetra[N-(pyridine-4-yl)benzamidium] porphyrin (A.3), 5-mono-(4-pyridyl)-10,15,20-tris-(4-pyridylbenzamide)porphyrin (B.2) and 5-mono-(4-methylpyridinium)-10,15,20-tris-(4-pyridiniumbenzamide)porphyrin (B.3) were synthesised. The compounds were successfully characterised through UV-Vis, Emission, 1H NMR, and ESI-HRMS techniques. To evaluate the effect of this combination of directly conjugated and non-conjugated pyridyl/cationic pyridinium groups on the porphyrin macrocycle, the efficacy of the synthesised compounds was compared to a known standard 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP). These compounds show better efficacy (IC50's ranging between 0.66±0.04µM to 3.71±1.01µM) against A549 (human epithelial adenocarcinoma lung cancer) cell line under in vitro photodynamic conditions in comparison to MDA-MB-231 (breast cancer) (IC50's ranging between 3.7±0.087µM to 12.1±0.12µM) and Pa-1 (ovarian cancer) (IC50's ranging between 17.9±0.01µM to 42.45±0.02µM) cell lines. It was found that B.3, having a pyridinium group attached to the meso-position of the macrocycle along with three distal cationic pyridinium groups, independent of the porphyrinic electron delocalisation cycle, showed better photocytotoxic efficacy (IC50=0.66±0.04µM, A549 lung cancer cell line) and higher potential to promote apoptosis and hence better efficacy as PS towards cancer photodynamic therapy (PDT). The PDT activity of B.3 was further verified and established by various biological assays, viz. Annexin V assay, cell cycle assay, and reactive oxygen species (ROS) activity assay.