Indium as a central metal enhances the photosensitizing efficacy of benzoporphyrin derivatives

Abstract

Compared to benzoporphyrin derivative-dimethyl ester (BPD-DME) and its 8-(1′-hexyloxy)ethyl analog the corresponding In(III) complexes showed enhanced in vitro photosensitizing efficacy in Colon26 tumor cells, which could be due to their higher singlet oxygen producing ability. In both organic (methanol) and aqueous Bovine Calf Serum (17% BCS) solutions the metalated analogs were significantly more stable than the parent photosensitizers. Presence of Indium as a central metal gave 13–25 nm hypsochromic shift to the long wavelength absorption band with reduced absorption and fluorescence intensity. The insertion of metal did not produce any difference in intracellular localization of the photosensitizers and were mainly localized in mitochondria.

Brazilian Green Propolis Extract Synergizes with Protoporphyrin IX-mediated Photodynamic Therapy via Enhancement of Intracellular Accumulation of Protoporphyrin IX and Attenuation of NF-κB and COX-2

“…The tumor-selective effects of the PDT are based on the preferential uptake and retention of the photosensitizer in the tumor [ 42 ]. The intracellular uptake and accumulation of photosensitizers has been a major problem in PDT especially when treating large solid tumors [ 43 , 44 ].…”

Biotinylated Chlorin and Its Zinc and Indium Complexes: Synthesis and In Vitro Biological Evaluation for Photodynamic Therapy

“…Attachment of a linker bridging a fluorophore to a vitamin folic acid was shown by other groups to enhance aqueous solubility and selectivity when tested in folate-receptor enriched human nasopharyngeal epidermoid carcinoma KB cells [32]. Previous studies also demonstrated that zinc [30,33,34,35,36] and indium [31,37,38] metal coordination to chlorins enhances in vitro oxidative cell damage and higher singlet oxygen production, respectively.…”

Mechanistics and photo‐energetics of macrocycles and photodynamic therapy: An overview of aspects to consider for research

“…Porphyrazine co‐ordination with Zn(II), Co(II), Ni(II), Pd(II), Gd(III), Mg(II) and Cu(II) has also been detailed . Conversely, research associating metal ions to the large class of chlorin‐based Ps for PDT are not common with the few reported studies including benzoporphyrins complexed to In(III), Pd(II) and Pt(II), bacteriochlorins complexed to Cu(II), Zn(II), Pd(II), NI(II), Cd(II), In(III) and Sn(II) and porphycenes complexed to Al(III) and Co(II) …”

“…Associating physiochemical and photophysical traits of the resulting Ps, whether newly created or modified from a parental macrocycle, is then required to be documented. These include physical structure and conformation, molecular weight, ionic charge, axial and equatorial ligand interaction tendencies, metal‐based and ligand‐based redox coupling, UV–vis spectral profile, Ps*(S 1 ) lifetime, ISC potential (low for PDD and high for PDT applications), Ps*(T 1 ) lifetime and quantum yield and O 2 − yield Solubility enhancement or solutions: These studies deal with taking either a novel Ps of potential therapeutic application or those unable for use due to solubility issues and either modifying them for increased environmental interaction or interaction with various natural or synthetic drug delivery systems.…”

“…For PDD, Ps are reported on their ability to solubilize within aqueous media simulating biological fluids, their cellular uptake efficiency and nature thereof (passive versus active), their intracellular localization points for knowledge of the targeted areas, their potential unwanted dark cytotoxicity, their potential to fluoresce following excitation within a given tissue type and their ability to preferentially accumulate within a targeted tissue type . For PDT, analysis encompasses a number of topics including optimization of individual Ps and light excitation dosages that fall within non‐toxic parameters, establishing an efficient dosage combination to achieve a desired percentage of in vitro population damage (the particular cellular trait analysed is chosen at the discretion of the researcher), determining whether the damage inflicted is associated with homoeostatic stress or a photocytotoxic response, confirming the induction of proliferation arrest or cell death due to the PDT conditions, observing various critical biomarkers for identification of the particular cell death mode exhibited by the cells in treatment, and lastly, whether this cell death confers population eradication or resistance to repeated treatment regimes Recreation for in vivo success: These studies work with live animal models and clinical trials to deduce tissue selectivity of the Ps for maximal accumulation, sufficient solubilization and transport within biological fluids, light irradiation versus tissue depth penetration for both PDD and PDT, induction of secondary body responses to PDT such as immune system stimulation and vascular damage within the aberrant tissue region, detection of any unwanted Ps‐related stress to bystander organ systems and tissues and the comparative analyses of tumour reduction versus eradication against similar treatment regimes.…”