Enhancing the Anticancer Activity and Selectivity of Goniothalamin Using pH-Sensitive Acetalated Dextran (Ac-Dex) Nanoparticles: A Promising Platform for Delivery of Natural Compounds
| Autor: | Carolyne B. Braga, Valéria Helena Alves Cagnon, Larissa Akemi Kido, Celina de Almeida Lamas, Catia Ornelas, Ronaldo A. Pilli, Ellen Nogueira Lima |
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| Rok vydání: | 2020 |
| Předmět: |
0206 medical engineering
Biomedical Engineering 02 engineering and technology Biomaterials Mice chemistry.chemical_compound In vivo Animals Humans Cytotoxicity Chemistry technology industry and agriculture In vitro toxicology Dextrans Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology 020601 biomedical engineering In vitro Dextran Pyrones Cancer cell Drug delivery cardiovascular system Biophysics Nanoparticles Nanomedicine 0210 nano-technology circulatory and respiratory physiology |
| Zdroj: | ACS Biomaterials Science & Engineering. 6:2929-2942 |
| ISSN: | 2373-9878 |
| DOI: | 10.1021/acsbiomaterials.0c00057 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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