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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: JOURNAL OF BIOMEDICAL NANOTECHNOLOGY; v. 17, n. 7, p. 1320-1329, JUL 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 11/23895-8 - Characterization and control of cellular internalization process of nanoparticles
• Grantee: Dayane Batista Tada
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 15/05980-9 - Antitumoral activity induced by peptides from transcription factor Brn-2 in murine and human melanoma
• Grantee: Denise Costa Arruda
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/01697-6 - Synthesis and functionalization of bimetallic nanoparticles for application in photodynamic therapy of cancer
• Grantee: Dayane Batista Tada
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/11972-7 - Analysis of Protein Expression Regulated by the Brn-2 Transcription Factor in Cells treated with Peptides-Derived from POU Domain of Brn-2 and Determination of the Internalization and Cell Localization of this Peptide
• Grantee: Denise Costa Arruda
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/51423-0 - Bioactive peptides and peptidases: biological and immunobiological activities in infectious diseases and cancer
• Grantee: Luiz Rodolpho Raja Gabaglia Travassos
• Support Opportunities: Research Projects - Thematic Grants