Intracellular Targeting of Poly Lactic-Co-Glycolic Acid Nanoparticles by Surface Functionalization with Peptides

Autor(es)

de Oliveira, Thais Dolzany ^[1] ; Travassos, Luiz R. ^[2] ; Arruda, Denise Costa ^[1] ; Tada, Dayane Batista ^[3]

Afiliação do(s) autor(es)

^[1] Univ Mogi das Cruzes, UMC, Integrated Grp Biotechnol, BR-08780911 Mogi Das Cruzes, SP - Brazil

^[2] Fed Univ Sao Paulo UNIFESP, Expt Oncol Unit UNONEX, BR-04023062 Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Inst Sci & Technol, BR-12231280 Sao Jose Dos Campos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF BIOMEDICAL NANOTECHNOLOGY; v. 17, n. 7, p. 1320-1329, JUL 2021.
• Citações Web of Science: 0

Resumo

Nanoparticles (NPs) are a promising strategy for delivering drugs to specific sites because of their tunable size and surface chemistry variety. Among the available materials, NPs prepared with biopolymers are of particular interest because of their biocompatibility and controlled release of encapsulated drugs. Poly lactic-co-glycolic acid (PLGA) is one of the most widely used biopolymers in biomedical applications. In addition to material choice modulation of the interaction between NPs and biological systems is essential for the safety and effective use of NPs. Therefore, this work focused on evaluating different surface functionalization strategies to promote cancer cell uptake and intracellular targeting of PLGA NPs. Herein, cell-penetrating peptides (CPPs) were shown to successfully drive PLGA NPs to the mitochondria and nuclei. Furthermore, the functionalization of PLGA NPs with peptide AC-1001 H3 (GQYGNLWFAY) was proven to be useful for targeting actin filaments. The PLGA NPs cell internalization mechanism by B16F10-Nex2 cells was identified as caveolae-mediated endocytosis, which could be inhibited by the presence of methyl-/3-cyclodextrin. Notably, when peptide IP: 14.98 160.66 O M 30 Aug 2021 11 0023 C (CVNHPAFAC) was used to functionalize PLGA NPs, none of the tested inhibitors could avoid cell internalization of Copyright: Amercan Scientiic Publishers PLGA NPs. Therefore, we suggest this peptide asa promising surface modification agent for enhancing drug delivery to Delivered by Ingena cancer cells. Finally, PLGA NPs showed slow release kinetics and low cytotoxic profile, which, combined with the surface functionalization strategies addressed in this study, highlight the potential of PLGA NPs as a drug delivery platform for improving cancer therapy. (AU)

• Processo FAPESP: 11/23895-8 - Caracterização e controle de mecanismos de internalização celular de nanopartículas
• Beneficiário: Dayane Batista Tada
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 15/05980-9 - Determinação da atividade antitumoral induzida por peptídeos derivados do fator de transcrição Brn-2 em melanoma murino e humano
• Beneficiário: Denise Costa Arruda
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/01697-6 - Síntese e funcionalização de nanopartículas bimetálicas para aplicação na terapia fotodinâmica de câncer
• Beneficiário: Dayane Batista Tada
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/11972-7 - Análise da Expressão de Proteínas Reguladas pelo Fator de Transcrição Brn-2 em Células Tratadas com Peptídeos Derivados do Domínio POU da Proteína Brn-2 e Determinação da Internalização e Localização Celular desses Peptídeos
• Beneficiário: Denise Costa Arruda
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/51423-0 - Peptídeos bioativos e peptidases: atividades biológicas e imunobiológicas em doenças infecciosas e no câncer
• Beneficiário: Luiz Rodolpho Raja Gabaglia Travassos
• Modalidade de apoio: Auxílio à Pesquisa - Temático