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Eur J Pharm Biopharm ; 157: 221-232, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33130338

RESUMO

Gold nanoparticle (AuNP)-based systems have been extensively investigated as diagnostic and therapeutic agents due to their tunable properties and easy surface functionalization. Upon cell uptake, AuNPs present an inherent cell impairment potential based on organelle and macromolecules damage, leading to cell death. Such cytotoxicity is concentration-dependent and completely undesirable, especially if unspecific. However, under non-cytotoxic concentrations, internalized AuNPs could potentially weaken cells and act as antitumor agents. Therefore, this study aimed to investigate the antitumor effect of ultrasmall AuNPs (~3 nm) stabilized by the anionic polysaccharide gum arabic (GA-AuNPs). Other than intrinsic cytotoxicity, the focus was downregulation of cancer hallmarks of aggressive tumors, using a highly metastatic model of melanoma. We first demonstrated that GA-AuNPs showed excellent stability under biological environment. Non-cytotoxic concentrations to seven different cell lines, including tumorigenic and non-tumorigenic cells, were determined by standard 2D in vitro assays. Gold concentrations ≤ 2.4 mg L-1 (16.5 nM AuNPs) were non-cytotoxic and therefore chosen for further analyses. Cells exposed to GA-AuNPs were uptaken by melanoma cells through endocytic processes. Next we described remarkable biological properties using non-cytotoxic concentrations of this nanomaterial. Invasion through an extracellular matrix barrier as well as 3D growth capacity (anchorage-independent colony formation and spheroids growth) were negatively affected by 2.4 mg L-1 GA-AuNPs. Additionally, exposed spheroids showed morphological changes, suggesting that GA-AuNPs could penetrate into the preformed tumor and affect its integrity. All together these results demonstrate that side effects, such as cytotoxicity, can be avoided by choosing the right concentration, nevertheless, preserving desirable effects such as modulation of key tumor cell malignancy features.


Assuntos
Antineoplásicos/farmacologia , Movimento Celular/efeitos dos fármacos , Compostos de Ouro/farmacologia , Melanoma Experimental/tratamento farmacológico , Nanopartículas Metálicas , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Estabilidade de Medicamentos , Endocitose , Compostos de Ouro/química , Compostos de Ouro/metabolismo , Compostos de Ouro/toxicidade , Goma Arábica/química , Humanos , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Camundongos , Nanomedicina , Invasividade Neoplásica , Metástase Neoplásica , Tamanho da Partícula , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
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