An engineered POSS drug delivery system for copper(ii) anticancer metallodrugs in a selective application toward melanoma cells

Author(s)

Vieira, Eduardo Guimaraes ; de Paiva, Raphael Enoque Ferraz ; Miguel, Rodrigo Bernardi ; de Oliveira, Ana Paula Araujo ; Bagatelli, Felipe Franco de Melo ; Oliveira, Carla Columbano ; Tuna, Floriana ; Ferreira, Ana Maria da Costa

• Document type: Journal article
• Source: DALTON TRANSACTIONS; v. 53, n. 30, p. 15-pg., 2024-06-26.

Abstract

In this work, a polyhedral silsesquioxane (POSS) was used as an engineered drug delivery system for two oxindolimine-copper(ii) anticancer complexes, [Cu(isaepy)](+) and [Cu(isapn)](+). The interest in hybrid POSS comes from the necessity of developing materials that can act as adjuvants to improve the cytotoxicity of non-soluble metallodrugs. Functionalization of POSS with a triazole ligand (POSS-atzac) permitted the anchorage of such copper complexes, producing hybrid materials with efficient cytotoxic effects. Structural and morphological characterizations of these copper-POSS systems were performed by using different techniques (IR, NMR, thermogravimetric analysis). A combination of continuous-wave (CW) and pulsed EPR (HYSCORE) spectroscopies conducted at the X-band have enabled the complete characterization of the coordination environment of the copper ion in the POSS-atzac matrix. Additionally, the cytotoxic effects of the loaded materials, [Cu(isapn)]@POSS-atzac and [Cu(isaepy)]@POSS-atzac, were assessed toward melanomas (SK-MEL), in comparison to non-tumorigenic cells (fibroblast P4). Evaluation of their nuclease activity or ability to facilitate cleavage of DNA indicated concentrations as low as 0.6 mu g mL(-1), while complete DNA fragmentation was observed at 25 mu g mL(-1). By using adequate scavengers, investigations on active intermediates responsible for their cytotoxicity were performed, both in the absence and in the presence of ascorbate as a reducing agent. Based on the observed selective cytotoxicity of these materials toward melanomas, investigations on the reactivity of these complexes and corresponding POSS-materials with melanin, a molecule that contributes to melanoma resistance to chemotherapy, were carried out. Results indicated the main role of the binuclear copper species, formed at the surface of the silica matrix, in the observed reactivity and selectivity of these copper-POSS systems. (AU)

• FAPESP's process: 20/00901-1 - Posttranscriptional control of gene expression: pre-rRNA processing, mRNA degradation, splicing and snoRNP assembly in Saccharomyces cerevisiae
• Grantee: Carla Columbano de Oliveira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/21070-5 - Vibrational spectroscopy with spatial resolution
• Grantee: Mauro Carlos Costa Ribeiro
• Support Opportunities: Research Projects - Thematic Grants
• 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 Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 16/16735-8 - Imobilization of potential metallopharmaceuticals in inorganic and organic matrices for modified delivery
• Grantee: Eduardo Guimarães Vieira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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 Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 18/21537-6 - Polydentate imine ligands as modulators of copper reactivity in inflammation-related diseases and in bioorthogonal coupling reactions
• Grantee: Raphael Enoque Ferraz de Paiva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral