In vitro study of the potential of piperine encapsulated in metal-organic frameworks with surface modification for the treatment of breast cancer

Author(s)

Christian Rafael Quijia Quezada

• Document type: Doctoral Thesis
• Press: Araraquara. 2023-07-18.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara
• Defense date: 2023-07-11
• Advisor: Marlus Chorilli

Abstract

Breast cancer is one of the leading causes of death among women with cancer worldwide, triggering the search for more effective chemotherapy treatments. Among the compounds with chemotherapeutic potential, piperine (PIP) stands out as promising due to its antitumor activity in breast cancer cell lines. However, the introduction of this compound in preclinical studies has been limited due to its toxicity. Metal-organic frameworks (MOFs), including MIL-100 (Fe), represent an attractive platform as drug delivery systems and can be employed to improve the bio-pharmaceutical properties of this molecule. Additionally, one engineering strategy is the modification of nanostructures with natural materials, such as macrophage membranes (MM) or chitosan (CHI), which are used as a camouflage system against the immune system within the body, providing resistance to degradation and controlled release. Inspired by these scientific and technological advancements, the present study aims to evaluate the potential of PIP encapsulated in MOFs coated with MM or CHI for-breast cancer treatment. In this research, we report the successful synthesis of nanosystems based on MIL-100(Fe) containing piperine coated with MM (MM@PIP@MIL-100(Fe)) or with CHI (CHI@PIP@MIL-100(Fe)) via microwave-assisted hydrothermal synthesis and impregnation method. X-ray diffraction analysis of MIL-100(Fe) and PIP@MIL-100(Fe) revealed the crystallinity of the materials, with particle sizes of 18.32 nm and 76.18 nm, respectively. Coating of vesicles for MM@PIP@MIL-100(Fe) was confirmed by electrophoresis (SDS-PAGE), demonstrating the presence of proteins on its surface. Chitosan coating on the MOF was confirmed by infrared spectroscopy. High-performance liquid chromatography (HPLC) was used to quantify PIP in the MOFs, showing an encapsulation efficiency of 95 ± 3%. Cytotoxicity assays on breast cancer cells such as MCF-7, SKBR3, MDA-MB-231, and BT549, using the materials PIP@MIL-100(Fe), MM@PIP@MIL-100(Fe), and CHII@PIP@MIL-100(Fe), revealed a higher cytotoxicity index compared to free piperine, with two to seventeen times higher median inhibitory concentration (IC50). In conclusion, this work undeniably demonstrates that these nanostructures hold promise for PIP-based therapies for breast cancer. (AU)

• FAPESP's process: 18/21119-0 - Evaluation of the potential of piperine encapsulated in metal-organic frameworks coated with macrophage membranes in the treatment of Breast Cancer
• Grantee: Christian Rafael Quijia Quezada
• Support Opportunities: Scholarships in Brazil - Doctorate