Contents lists available at ScienceDirect Materials Science & Engineering B journal homepage: www.elsevier.com/locate/mseb Atomic force microscopy and dark-toxicity pattern of unsymmetrical metallated porphyrins M(II)P-type as theranostics agents Radu Socoteanu a , Mihai Anastasescu a, ⁎ , Rica Boscencu b, ⁎ , Carolina Constantin c , Monica Neagu c,d,e a “Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 202 Splaiul Independentei, 060021 Bucharest, Romania b Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia St., 020956 Bucharest, Romania c “Victor Babes” National Institute for Pathology and Biomedical Sciences, 99-101 Splaiul Independentei, 050096 Bucharest, Romania d Colentina University Hospital, 19-21 Stefan cel Mare Bld, 020125 Bucharest, Romania e Faculty of Biology, University of Bucharest, 91-95 Splaiul Independentei, 050095 Bucharest, Romania ARTICLE INFO Keywords: Porphyrins AFM Cell experiments Dark toxicity Theranostics ABSTRACT Two unsymmetrical metalloporphyrins, of M(II)P-type, Cu(II)-5-[(3,4-methylenedioxy)phenyl]-10,15,20–tris-(4- carboxymethylphenyl) porphyrin and Zn(II)-5-[(3,4-methylenedioxy)phenyl]-10,15,20–tris-(4-carbox- ymethylphenyl) porphyrin have been investigated by means of Atomic Force Microscopy (AFM) and in vitro cytotoxicity measurements. AFM studies emphasized the highly self-similarity of the investigated compounds on the basis of mean fractal dimension values. A specific morphology, consisting in alternative hillocks and valleys which have tens of nanometers, that are suitable for cell adhesion was observed. Short term as well as long term dark toxicity tests were performed on Human U937 cell line and Human peripheral mononuclear cells isolated from venous blood of normal volunteers and cancer patients. It was found that both short and long term in- cubation of U937 cells with Cu(II)P19.2 and Zn(II)P19.2 doesn’t distress cellular viability, sustaining the non- toxic outline of M(II)P-type series upon monocytic cell line. 1. Introduction Studies linking subjects as porphyrins, characterized mainly by atomic force microscopy (AFM) technique and their toxicological parameters gathered from in vitro cultured cell lines are rare, despite the importance of both these topics. Hence, the connection between these approaches is resulting especially in valuable empirical data connected to medicinal chemistry. Regarding this field, tremendous efforts are done for implementation of sophisticated, unconventional methods and techniques able to bring together the medical diagnosis and therapy (theranostics) with chemical fine synthesis of appropriate compounds as theranostics agents. Photodynamic therapy still represents a valuable approach together with many other modern oncological procedures. This technique used especially against cancer cells is based on photosensitizer type mole- cules which, in the presence of molecular oxygen and irradiated with visible light (red spectral range), are able to induce the reactive oxygen species (ROS) generation, particularly singlet oxygen ( 1 O 2 ). In line with a target medical application, a photosenzitizer com- pound should gather many specific structural and functional characteristics, such as: high purity, low dark cytotoxicity, good pho- tostability, high molar absorption coefficient in the spectral range where light penetration of tissue is good, high quantum yields of singlet oxygen generation and good clearance from the normal tissues. The amphyphilic structure of the photosensitizer is also determinant for its pharmacokinetics and pharmacodynamics behavior [1–6]. Accordingly, PDT is centered on porphyrins type structures used as photosenzitizers and a wide range of biomedical studies are meant to investigate their behavior and clinical applications. In addition to these, some works managed to inforce AFM as a versatile tool for topo- graphical (structural) characterization of porphyrins both as self-sus- tained nanomaterial but also connected to different surfaces [1–5], evaluating the morphology and textural properties, as well as self as- sembly capacity of many porphyrinic-type compounds [6–10]. In line with this, conductive probe atomic force microscopy ex- periments were designed to investigate how the molecular structure influences the selforganization, surface assembly, and conductive properties of cobaltacarborane porphyrins. It was observed that the number and placement of the cobaltacarborane ligands on the por- phyrin macrocycle affects the interactions that drive porphyrin self- https://doi.org/10.1016/j.mseb.2019.05.012 Received 1 October 2017; Received in revised form 18 February 2019; Accepted 15 May 2019 ⁎ Corresponding authors. E-mail addresses: manastasescu@icf.ro (M. Anastasescu), rboscencu@yahoo.com (R. Boscencu). Materials Science & Engineering B 245 (2019) 85–94 0921-5107/ © 2019 Elsevier B.V. All rights reserved. T