Evaluation of tumor growth remission in a murine model for subcutaneous solid tumors - Benefits of associating the antitumor agent crotamine with mesoporous nanosilica particles to achieve improved dosing frequency and efficacy

Author(s)

Oyadomari, William Yoshio ; Anthero, Gabriel Lessa ; Silva, Marcos R. de A. ; Porta, Lucas C. ; Oliveira, Vitor ; Reid, Paul F. ; Sant'Anna, Osvaldo A. ; Alves, Wendel A. ; Nani, Joao, V ; Hayashi, Mirian Akemi Furuie

• Document type: Journal article
• Source: International Journal of Pharmaceutics; v. 646, p. 8-pg., 2023-10-05.

Abstract

Crotamine is a highly cationic polypeptide first isolated from South American rattlesnake venom, which exhibits affinity for acidic lysosomal vesicles and proliferating cells. This cationic nature is pivotal for its in vitro cyto-toxicity and in vivo anticancer actions. This study aimed to enhance the antitumor efficacy of crotamine by associating it with the mesoporous SBA-15 silica, known for its controlled release of various chemical agents, including large proteins. This association aimed to mitigate the toxic effects while amplifying the pharmaco-logical potency of several compounds. Comprehensive characterization, including transmission electron micro-scopy (TEM), dynamic light scattering (DLS), and zeta potential analysis, confirmed the successful association of crotamine with the non-toxic SBA-15 nanoparticles. The TEM imaging revealed nanoparticles with a nearly spherical shape and variations in uniformity upon crotamine association. Furthermore, DLS showed a narrow unimodal size distribution, emphasizing the formation of small aggregates. Zeta potential measurements indi-cated a distinct shift from negative to positive values upon crotamine association, underscoring its effective adsorption onto SBA-15. Intraperitoneal or oral administration of crotamine:SBA-15 in a murine melanoma model suggested the potential to reduce the frequency of crotamine doses without compromising efficacy. Interestingly, while the oral route enhanced the antitumor efficacy of crotamine, pH-dependent release from SBA-15 was observed. Thus, associating crotamine with SBA-15 could reduce the overall required dose to inhibit solid tumor growth, bolstering the prospect of crotamine as a potent anticancer agent. (AU)

• FAPESP's process: 19/09207-3 - Study of molecular and cellular mechanisms in mental disorders
• Grantee: João Victor Silva Nani
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/01107-7 - Study to optimize the use of crotamine as a theranostic in the therapy of human diseases: cancer, metabolic syndrome and renal dysfunction
• Grantee: Mirian Akemi Furuie Hayashi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/00527-8 - Enzymatic activity of oligopeptidases Ndel1 and/or ACE in plasma or blood serum of patients with Depression
• Grantee: Larissa Ribino Parra
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 17/02413-1 - Validation of crotamine as a biomarker and evaluation of its potential use in the therapy of human diseases
• Grantee: Mirian Akemi Furuie Hayashi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/08287-3 - Effect of crotamine on glucose uptake by brown adipose tissue: evaluation in an experimental model with 18FDG PET
• Grantee: Marcelo Tatit Sapienza
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/03297-3 - Exploring the molecular and cellular mechanism(s) underlying neurodevelopmental disorders: investigating the role(s) of Nuclear Distribution Element like-1 (Ndel1)
• Grantee: João Victor Silva Nani
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 19/13112-8 - Study of molecular and cellular mechanisms involved in mental disorders: clinical and animal models analysis
• Grantee: Mirian Akemi Furuie Hayashi
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/50891-1 - INCT 2014: Translational Medicine
• Grantee: Jaime Eduardo Cecilio Hallak
• Support Opportunities: Research Projects - Thematic Grants