Effect of structural variation on tumor targeting efficacy of cationically charged porphyrin derivatives: Comparative in-vitro and in-vivo evaluation for possible potential in PET and PDT.

Autor: Guleria M; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India., Suman SK; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India., Mitra JB; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India., Shelar SB; Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India., Amirdhanayagam J; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India., Sarma HD; Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India., Dash A; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India., Das T; Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai, 400094, India. Electronic address: tdas@barc.gov.in.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2021 Mar 05; Vol. 213, pp. 113184. Date of Electronic Publication: 2021 Jan 16.
DOI: 10.1016/j.ejmech.2021.113184
Abstrakt: tetracationic (TMPyP) and tricationic porphyrin (TriMPyCOOHP) derivatives were synthesized, characterized and investigated for binding with DNA by Isothermal Titration Calorimetry as well as by UV-Vis spectroscopy in order to study the effect of structural variation on tumor targeting efficacy of cationically charged porphyrin derivatives. Fluorescence cell imaging studies performed in cancer cell lines corroborated the findings of aforementioned studies. Photocytotoxicity experiments in A549 cell lines revealed relatively higher light dependent cytotoxic effects exerted by TMPyP compared to TriMPyCOOHP. In-vivo experiments in tumor bearing animal model revealed relatively longer retention of 68 Ga-TMPyP in tumorous lesion compared to that of 68 Ga-TriMPyCOOHP. The study reveals that removal of one of the positive charges of the tetracationic porphyrin derivatives significantly reduces their DNA binding ability and cytotoxicity as well as brings changes in the pharmacokinetic pattern and tumor retention in small animal model.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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