Functionalized nanoparticles as adjuvant to increase the cytotoxicity of metallodrugs toward tumor cells

Author(s):Show less -

Vieira, Eduardo Guimaraes ^[1] ; Miguel, Rodrigo Bernardi ^[1] ; da Silva, Daniel Rodrigues ^[1] ; Fazzi, Rodrigo Boni ^[1] ; Alves de Couto, Ricardo Alexandre ^[1] ; Marin, Jayr Henrique ^[1] ; Arruda Temperini, Marcia Laudelina ^[1] ; Shinohara, Jorge da Silva ^[1] ; Toma, Henrique Eisi ^[1] ; Russo, Lilian Cristina ^[2] ; Magalhaes, Yuli Thamires ^[2] ; Dias Filho, Newton Luiz ^[3] ; Forti, Fabio Luiz ^[2] ; da Costa Ferreira, Ana Maria ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05508000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo State UNESP, Dept Chem & Phys, BR-15385000 Ilha Solteira, SP - Brazil

• Document type: Journal article
• Source: NEW JOURNAL OF CHEMISTRY; v. 43, n. 1, p. 386-398, JAN 7 2019.
• Web of Science Citations: 1

Abstract

Functionalized MCM-41 is a class of new nanoporous biomaterials extensively studied as drug carriers of a diversity of therapeutic agents due to its suitable properties. In the present study, two oxindolimine complexes based on copper(ii) and zinc(ii) were immobilized in two selective delivery systems, namely, unmodified and modified MCM-41, which can act as carriers of water-insoluble anticancer metallodrugs. Morphological and structural characterizations of these materials were accomplished, and their cytotoxic effect was evaluated on three different cancer cell lines, SKMEL-147, SKMEL-05 and HeLa, in comparison to a non-tumor cell line (fibroblast P4). Cytotoxicity assays showed that both complexes coordinated to the modified matrix were more active and selective than those immobilized into the unmodified matrix, particularly toward SKMEL-147 cells. In contrast, P4 cells were much less affected by the presence of these compounds, with very high IC50 values. Further, the release of the complexes from these materials was monitored in vitro by X-ray fluorescence, which indicated a significant delivery after 2 h at 37 degrees C. By using CytoViva images, it was possible to observe the presence of such nanoparticles inside the cells, as well as the formation of apoptotic bodies due to the action of these antitumor compounds. A high damage on the nucleus was verified by comet and DNA cleavage assays, pointing to DNA as an important target of such metallodrugs. The matrices also contribute to the potential therapeutic action of these metal complexes, significantly increasing their cytotoxicity against melanoma and cervical carcinoma cells. (AU)

• FAPESP's process: 16/21070-5 - Vibrational spectroscopy with spatial resolution
• Grantee: Mauro Carlos Costa Ribeiro
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 16/16735-8 - Imobilization of potential metallopharmaceuticals in inorganic and organic matrices for modified delivery
• Grantee: Eduardo Guimarães Vieira
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 11/50318-1 - Development of compounds with pharmacological or medicinal interest and of systems for their transport, detection and recognition in biological media
• Grantee: Ana Maria da Costa Ferreira
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/21919-3 - Spectroscopic and magnetic characterization of metallo-pharmaceuticals immobilized in hybrid matrices for drug delivery
• Grantee: Eduardo Guimarães Vieira
• Support type: Scholarships abroad - Research Internship - Post-doctor