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Enhancing the Anticancer Activity and Selectivity of Goniothalamin Using pH-Sensitive Acetalated Dextran (Ac-Dex) Nanoparticles: A Promising Platform for Delivery of Natural Compounds

Texto completo
Autor(es):
Braga, Carolyne B. [1] ; Kido, Larissa A. [2] ; Lima, Ellen N. [2] ; Lamas, Celina A. [2] ; Cagnon, Valeria H. A. [2] ; Ornelas, Catia [1] ; Pilli, Ronaldo A. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, UNICAMP, Dept Organ Chem, Inst Chem, BR-13083970 Campinas, SP - Brazil
[2] Univ Estadual Campinas, UNICAMP, Dept Struct & Funct Biol, Inst Biol, BR-13083865 Campinas, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: ACS BIOMATERIALS SCIENCE & ENGINEERING; v. 6, n. 5, SI, p. 2929-2942, MAY 2020.
Citações Web of Science: 0
Resumo

Goniothalamin GTN), a natural compound isolated from Goniothalamus species, has previously demonstrated cytotoxic activity against several cancer cell lines. However, similarly to many natural and synthetic anticancer compounds, GTN presents toxicity toward some healthy cells and low aqueous solubility, decreasing its bioavailability and precluding its application as an antineoplastic drug. In our efforts to improve the pharmacokinetic behavior and selectivity of GTN against cancer cells, we developed a polymeric nanosystem, in which rac-GTN was encapsulated in pH-responsive acetalated dextran (Ac-Dex) nanoparticles (NPs) with high loadings of the bioactive compound. Dynamic light scattering (DLS) analysis showed that the nanoparticles obtained presented a narrow size distribution of around 100 nm in diameter, whereas electron microscopy (EM) images showed nanoparticles with a regular spherical morphology in agreement with the size range obtained by DLS. Stability and release studies indicated that the GTN@Ac-Dex NPs presented high stability under physiological conditions (pH 7.4) and disassembled under slightly acidic conditions (pH 5.5), releasing the rac-GTN in a sustained manner. In vitro assays showed that GTN@Ac-Dex NPs significantly increased cytotoxicity and selectivity against cancer cells when compared with the empty Ac-Dex NPs and the free rac-GNT. Cellular uptake and morphology studies using MCF-7 cells demonstrated that GTN@Ac-Dex NPs are rapidly internalized into the cancer cells, causing cell death. In vivo investigation confirmed the efficient release of rac-GTN from GTN@Ac-Dex NPs, resulting in the delay of prostate cancer progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Furthermore, liver histopathology evaluation after treatment with GTN@Ac-Dex NPs showed no evidence of toxicity. Therefore, the in vitro and in vivo findings suggest that the Ac-Dex NPs are a promising nanosystem for the sustained delivery of rac-GTN into tumors. (AU)

Processo FAPESP: 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas
Beneficiário:Licio Augusto Velloso
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 17/06146-8 - Desenvolvimento de nanocarregadores baseados em dendrímeros e nanopartículas poliméricas para a vetorização seletiva da goniotalamina, piplartina e monastrol
Beneficiário:Carolyne Brustolin Braga
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 08/57906-3 - Instituto Nacional de Fotônica Aplicada à Biologia Celular - INFABIC
Beneficiário:Hernandes Faustino de Carvalho
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 19/13104-5 - Planejamento e síntese de inibidores baseado em alvo biológico: o caso das quinases negligenciadas
Beneficiário:Ronaldo Aloise Pilli
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/02093-0 - Desenvolvimento de novos nanomateriais para aplicações em nanomedicina
Beneficiário:Cátia Cristina Capêlo Ornelas Megiatto
Linha de fomento: Auxílio à Pesquisa - Regular