A novel strategy for glioblastoma treatment combining alpha-cyano-4-hydroxycinnamic acid with cetuximab using nanotechnology-based delivery systems

Author(s)

Ferreira, Natalia N. ; Granja, Sara ; Boni, Fernanda Isadora ; Ferreira, Leonardo M. B. ; Reis, Rui M. ; Baltazar, Fatima ; Gremiao, Maria Palmira D.

• Document type: Journal article
• Source: DRUG DELIVERY AND TRANSLATIONAL RESEARCH; v. 10, n. 3, p. 16-pg., 2020-01-24.

Abstract

Combination therapy that uses multiple drugs against different molecular targets should be considered as interesting alternatives for treating complex diseases such as glioblastoma (GBM). Drugs like alpha-cyano-4-hydroxycinnamic acid (CHC) and the monoclonal antibody cetuximab (CTX) are already explored for their capacity to act against different hallmarks of cancer. Previous reports suggest that the simultaneous use of these drugs, as a novel combining approach, might result in additive or synergistic effects. Therefore, advances in nanotechnology-based delivery systems will inevitably bring nano-mediated therapeutic gains to the proposed combination since they enable the association of different drugs into a single carrier. The current study provides indications that the new dual therapeutic strategy proposed, in association with nanotechnology, provides significative improvements when compared to the use of isolated drugs. Nanotechnological tools were employed by developing polymeric nanoparticles based on poly(lactic-co-glycolic acid) and chitosan for CHC encapsulation. Furthermore, these structures were conjugated with CTX by supramolecular forces. In summary, the encapsulation of the CHC drug into the nanoparticles increased its individual therapeutic capacity. In addition, conjugation with CTX seemed to enhance therapeutic efficacy, especially for U251 GBM cells. In conclusion, developed nanostructured delivery systems exhibited a set of favorable attributes and potential to be applied as a promising new alternative for GBM treatment. (AU)

• FAPESP's process: 18/04546-1 - Evaluation of synergic effect between CHC and cetuximab against glioblastoma using drug delivery systems
• Grantee: Natália Noronha Ferreira Naddeo
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 17/16324-0 - Mucoadhesive delivery systems for the release of drugs on intestinal mucosa
• Grantee: Maria Palmira Daflon Gremião
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/09671-3 - Nanostructured multifunctional systems for drug controlled release through nasal route on glioblastomas treatment
• Grantee: Natália Noronha Ferreira Naddeo
• Support Opportunities: Scholarships in Brazil - Doctorate