Multicellular Quadruple Colorectal Cancer Spheroids as an In Vitro Tool for Antiangiogenic Potential Evaluation of Nanoparticles

Author(s)

Carvalho, Suzana ; Silveira, Maria Jose ; Domingues, Mariana ; Ferreira, Barbara ; Pereira, Catarina Leite ; Gremiao, Maria Palmira ; Sarmento, Bruno

• Document type: Journal article
• Source: ADVANCED THERAPEUTICS; v. N/A, p. 11-pg., 2023-01-22.

Abstract

The encapsulation of bevacizumab (BVZ), angiogenesis inhibitor antibody, into nanocarriers is explored aiming at enhancing its efficacy in colorectal cancer (CRC) treatment while eliminating potential side effects. Still, the translation of such nanomedicines into clinics is not straightforward owing to their preclinical screening in simplistic models, that do not mimic the complexity and heterogeneity of the CRC microenvironment. Herein, the development of a multicellular spheroid of CRC as an advanced preclinical model of CRC capable of screening the antiangiogenic potential of novel nanomedicines is proposed. For that, a quadruple co-culture is established through the combination of HCT116 cells, human pulmonary microvascular endothelial cell (HPMEC), fibroblasts, and macrophages. It is demonstrated that the developed model displays intrinsic CRC features, such as the organization of cells, expression of tumor microenvironment, extracellular matrix, and the formation of a necrotic core. Moreover, the model is shown to be composed mostly of HCT116 (93%), followed by hypoxia-inducible factor (3%), HPMEC (3%), and macrophages (1%). Gellan gum/chitosan nanoparticles encapsulating BVZ exhibit superior antiangiogenic properties when compared to free BVZ. Overall, the developed nanoparticles can further be explored as a promising approach in CRC treatment. (AU)

• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/10761-5 - Multifunctional systems for the specific colonoscopy of bevacizumab for the treatment of Colorectal Cancer
• Grantee: Suzana Gonçalves Carvalho
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 21/08699-0 - In vitro evaluation of biocompatibility, intestinal permeability, and anticancer properties of multifunctional systems intended for colonic release of bevacizumab in the treatment of colorectal cancer
• Grantee: Suzana Gonçalves Carvalho
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate