Department of Chemistry and Pharmacy, Laboratory of Nanomedicine, University of Sassari , 07100 Sassari, Italy.
Mol Pharm. 2013 Oct 7;10(10):3871-81. doi: 10.1021/mp400342f. Epub 2013 Sep 4.
Nanoencapsulation of antiproliferative and chemopreventive phytoalexin trans-resveratrol (RSV) is likely to provide protection against degradation, enhancement of bioavailability, improvement in intracellular penetration and control delivery. In this study, polymeric nanoparticles (NPs) encapsulating RSV (nano-RSV) as novel prototypes for prostate cancer (PCa) treatment were designed, characterized and evaluated using human PCa cells. Nanosystems, composed of a biocompatible blend of poly(epsilon-caprolactone) (PCL) and poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol) conjugate (PLGA-PEG-COOH), were prepared by a nanoprecipitation method, and characterized in terms of morphology, particle size and zeta potential, encapsulation efficiency, thermal analyses, and in vitro release studies. Cellular uptake of NPs was then evaluated in PCa cell lines DU-145, PC-3, and LNCaP using confocal fluorescence microscopy, and antiproliferative efficacy was assessed using MTT assay. With encapsulation efficiencies ranging from 74% to 98%, RSV was successfully loaded in PCL:PLGA-PEG-COOH NPs, which showed an average diameter of 150 nm. NPs were able to control the RSV release at pH 6.5 and 7.4, mimicking the acidic tumoral microenvironment and physiological conditions, respectively, with only 55% of RSV released within 7 h. In gastrointestinal simulated fluids, NPs released about 55% of RSV in the first 2 h in acidic medium, and their total RSV content within the subsequent 5 h at pH 7.4. Confocal fluorescence microscopy observations revealed that NPs were efficiently taken up by PCa cell lines. Furthermore, nano-RSV significantly improved the cytotoxicity compared to that of free RSV toward all three cell lines, at all tested concentrations (from 10 μM to 40 μM), proving a consistent sensitivity toward both the androgen-independent DU-145 and hormone-sensitive LNCaP cells. Our findings support the potential use of developed nanoprototypes for the controlled delivery of bioactive RSV for PCa chemoprevention/chemotherapy.
纳米封装具有抗增殖和化学预防作用的植物抗毒素白藜芦醇（RSV）可能提供保护，防止降解，提高生物利用度，改善细胞内渗透和控制释放。在这项研究中，设计了新型前列腺癌（PCa）治疗用聚合物纳米颗粒（NPs）包裹 RSV（纳米 RSV）作为原型，并用人前列腺癌细胞进行了表征和评估。纳米系统由生物相容性的聚己内酯（PCL）和聚（D，L-乳酸-共-乙醇酸）-聚乙二醇-羧酸（PLGA-PEG-COOH）的混合物组成，通过纳米沉淀法制备，并在形态，粒径和ζ电位，包封效率，热分析和体外释放研究方面进行了表征。然后使用共聚焦荧光显微镜评估 NP 在 PCa 细胞系 DU-145、PC-3 和 LNCaP 中的摄取，并用 MTT 测定法评估抗增殖作用。包封效率在 74%到 98%之间，RSV 成功地装载在 PCL：PLGA-PEG-COOH NPs 中，平均粒径为 150nm。NP 能够在 pH6.5 和 7.4 下控制 RSV 的释放，分别模拟酸性肿瘤微环境和生理条件，在 7 小时内仅释放 55%的 RSV。在胃肠道模拟液中，NP 在酸性介质中的前 2 小时内释放了约 55%的 RSV，在随后的 5 小时内 pH7.4 时，NP 中的总 RSV 含量。共聚焦荧光显微镜观察表明，NP 被 PCa 细胞系有效摄取。此外，与游离 RSV 相比，纳米 RSV 显著提高了所有三种细胞系的细胞毒性，在所有测试浓度（从 10μM 到 40μM）下，对雄激素非依赖性 DU-145 和激素敏感性 LNCaP 细胞均具有一致的敏感性。我们的研究结果支持开发的纳米原型用于控制生物活性 RSV 用于 PCa 化学预防/化疗的传递。
