Marinheiro Diogo, Ferreira Bárbara J M L, Oskoei Párástu, Oliveira Helena, Daniel-da-Silva Ana L
Department of Chemistry & CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal.
Department of Biology & CESAM-Centre for Environmental and Marine Studies, University of Aveiro, 3810-193 Aveiro, Portugal.
Materials (Basel). 2021 Mar 12;14(6):1382. doi: 10.3390/ma14061382.
Chemotherapy has limited success in the treatment of malignant melanoma due to fast development of drug resistance and the low bioavailability of chemotherapeutic drugs. Resveratrol (RES) is a natural polyphenol with recognized preventive and therapeutic anti-cancer properties. However, poor RES solubility hampers its bioactivity, thus creating a demand for suitable drug delivery systems to improve it. This work aimed to assess the potential of RES-loaded mesoporous silica nanoparticles (MSNs) for human melanoma treatment. RES was efficiently loaded (efficiency > 93%) onto spheroidal (size~60 nm) MSNs. The encapsulation promoted the amorphization of RES and enhanced the release in vitro compared to non-encapsulated RES. The RES release was pH-dependent and markedly faster at pH 5.2 (acid environment in some tumorous tissues) than at pH 7.4 in both encapsulated and bulk forms. The RES release from loaded MSNs was gradual with time, without a burst effect, and well-described by the Weibull model. In vitro cytotoxicity studies on human A375 and MNT-1 melanoma cellular cultures showed a decrease in the cell viability with increasing concentration of RES-loaded MSNs, indicating the potent action of the released RES in both cell lines. The amelanotic cell line A375 was more sensitive to RES concentration than the melanotic MNT-1 cells.
由于耐药性的快速发展和化疗药物的低生物利用度，化疗在恶性黑色素瘤的治疗中成效有限。白藜芦醇（RES）是一种天然多酚，具有公认的预防和治疗抗癌特性。然而，RES的低溶解度阻碍了其生物活性，因此需要合适的药物递送系统来改善这一情况。这项工作旨在评估负载RES的介孔二氧化硅纳米颗粒（MSNs）在治疗人类黑色素瘤方面的潜力。RES被高效地负载（效率>93%）到球形（尺寸约60nm）的MSNs上。与未封装的RES相比，封装促进了RES的非晶化并增强了其体外释放。RES的释放在pH值为5.2（某些肿瘤组织中的酸性环境）时比在pH值为7.4时更快，且无论是封装形式还是散装形式均如此。负载MSNs的RES释放随时间逐渐进行，没有突释效应，并且能用威布尔模型很好地描述。对人类A375和MNT-1黑色素瘤细胞培养物进行的体外细胞毒性研究表明，随着负载RES的MSNs浓度增加，细胞活力下降，这表明释放的RES在两种细胞系中均具有强效作用。无黑色素细胞系A375比有黑色素的MNT-1细胞对RES浓度更敏感。
