Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment

Author:

Pires Indira C. B.1,Shuchi Samia I.2,Tostes Braulio de V. A.1ORCID,Santos Dayane K. D. do N.1,Burnett William L.3,Leonce Burke C.3,Harvey Omar R.3ORCID,Coffer Jeffery L.3ORCID,de Sousa Filho Idio Alves4,de Athayde-Filho Petrônio Filgueiras5,Junior Severino A.1,Mathis J. Michael2ORCID

Affiliation:

1. Department of Chemistry, Federal University of Pernambuco, Recife 50670-901, PE, Brazil

2. School of Biomedical Sciences, Departments of Microbiology, Immunology, and Genetics and Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA

3. Department of Chemistry and Biochemistry, Texas Christian University, Fort Worth, TX 76109, USA

4. Institute of Chemistry, Federal Rural University of Rio de Janeiro, Rio de Janeiro 23890-000, RJ, Brazil

5. Department of Chemistry, Federal University of João Pessoa, João Pessoa 58051-900, PB, Brazil

Abstract

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3⁺-MIH and its potential to enhance breast cancer management.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) of Brazil

Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco

Department of Microbiology, Immunology, and Genetics at the University of North Texas Health Science Center

Publisher

MDPI AG

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