Development of a multifunctional injectable composite aiming bone cancer treatment through hyperthermia and brachytherapy allied with bone repair

• Grant number: 20/00329-6
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2021
• End date: September 30, 2023
• Field of knowledge: Engineering - Biomedical Engineering - Bioengineering
• Principal Investigator: Juliana Marchi
• Grantee: Juliana Marchi
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated researchers: Ana Carolina Santos de Souza Galvão ; Francesco Baino ; Giselle Zenker Justo ; Guilherme Soares Zahn ; Joel Machado Junior ; Mitiko Saiki

Abstract

Bone cancer is a type of neoplasm in the bone tissue, and is associated with unbalanced bone tissue homeostasis, as well as it can be a result of a metastasis. In general, the tumor growth leads to side effects like pain and decrease in patient's life quality. This proposal aims the development of a multifunctional material that allies hyperthermia, brachytherapy and use of zoledronic acid for treatment of bone cancer. This project consist of to develop a PEO-PPO-PEO-based hydrogel matrix, which will be used to carrier holmium-166-containing biocompatible glass, magnetite nanoparticle and zoledronic acid. The magnetite nanoparticles will be used to treat cancer by magnetic hyperthermia. The 166Ho-containing biocompatible glass aims to treat cancer by brachytherapy, and to improve bone regeneration. The zoledronic acid aims to support bone regeneration and to induce the death of cancerous cells. The glasses will be obtained through sol-gel synthesis, and characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy coupled with an energy dispersive spectrometer (SEM-EDS) and solid state nuclear magnetic resonance (NMR). The magnetite nanoparticles will be obtained by thermal decomposition, and characterized by XRD, dynamic light scattering (DLS), and its magnetic properties evaluated in a vibrating sample magnetometer (VSM). Systems made of hydrogel, drug, 166Ho-containing biocompatible glass and magnetite nanoparticle will be characterized by DLS, differential scanning calorimetry (DSC), and their reology evaluated in a reometer in a cone-plate geometry. The radioactive properties suitable for brachytherapy will be determined by neutron activation, and the properties for hyperthermia will be measured under magnetic field. Drug release essay will be done under (or not) the presence of magnetic field, and the drug concentration determined through HPLC. Cell viability of all systems will be evaluated by MTT and Neutron Red stains. The osteogenic activity will be determined by alizarin red stain, and genes related to osteoconduction will be evaluated by qRT-PCR. At the end, of this project, it is expected to achieve a multifunctional system with suitable properties for bone cancer treatment and bone repair. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BORGES, ROGER; KAI, KAREN C.; LIMA, CASSIO A.; ZEZELL, DENISE M.; DE ARAUJO, DANIELE R.; MARCHI, JULIANA. Bioactive glass/poloxamer 407 hydrogel composite as a drug delivery system: The interplay between glass dissolution and drug release kinetics. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 206, OCT 2021. (20/00329-6, 16/16512-9)

BORGES, ROGER; FERREIRA, LETICIE M.; RETTORI, CARLOS; LOURENCO, ISABELLA M.; SEABRA, AMEDEA B.; MUELLER, FRANK A.; FERRAZ, EMANUELA PRADO; MARQUES, MARCIA M.; MIOLA, MARTA; BAINO, FRANCESCO; et al. Superparamagnetic and highly bioactive SPIONS/bioactive glass nanocomposite and its potential application in magnetic hyperthermia. BIOMATERIALS ADVANCES, v. 135, p. 15-pg., 2022-04-01. (20/00329-6, 11/19924-2, 16/16512-9)

BORGES, ROGER; PELOSINE, AGATHA MARIA; DE SOUZA, ANA CAROLINA SANTOS; MACHADO JR, JOEL; JUSTO, GISELLE ZENKER; GAMARRA, LIONEL FERNEL; MARCHI, JULIANA. Bioactive Glasses as Carriers of Cancer-Targeted Drugs: Challenges and Opportunities in Bone Cancer Treatment. MATERIALS, v. 15, n. 24, p. 25-pg., 2022-12-01. (20/00329-6, 16/16512-9)

BORGES, ROGER; ZAMBANINI, TELMA; PELOSINE, AGATHA MARIA; JUSTO, GISELLE ZENKER; SOUZA, ANA CAROLINA S.; MACHADO JR, JOEL; SCHNEIDER, JOSE FABIAN; DE ARAUJO, DANIELE R.; MARCHI, JULIANA. A colloidal hydrogel-based drug delivery system overcomes the limitation of combining bisphosphonates with bioactive glasses: in vitro evidence of a potential selective bone cancer treatment allied with bone regeneration. BIOMATERIALS ADVANCES, v. 151, p. 14-pg., 2023-08-01. (16/16512-9, 20/00329-6)

BAINO, FRANCESCO; MARCHI, JULIANA; BORGES, ROGER; VERNE, ENRICA. Holmium-doped 58S glass-derived foam-like scaffolds. Materials Letters, v. 341, p. 3-pg., 2023-03-22. (20/00329-6)