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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: ADVANCED THERAPEUTICS; v. N/A, p. 11-pg., 2023-01-22.

Resumo

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)

• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/10761-5 - Sistemas multifuncionais destinados à liberação cólon específica do bevacizumabe para o tratamento do Câncer Colorretal
• Beneficiário: Suzana Gonçalves Carvalho
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 21/08699-0 - Avaliação in vitro da biocompatibilidade, permeabilidade intestinal e propriedades anticâncer de sistemas multifuncionais destinados à liberação colônica do bevacizumabe no tratamento do câncer colorretal
• Beneficiário: Suzana Gonçalves Carvalho
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado