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首页> 美国卫生研究院文献>other >Resveratrol-Loaded Nanoparticles Based on Poly(epsilon-caprolactone) and Poly(dl-lactic-co-glycolic acid)–Poly(ethylene glycol) Blend for Prostate Cancer Treatment
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Resveratrol-Loaded Nanoparticles Based on Poly(epsilon-caprolactone) and Poly(dl-lactic-co-glycolic acid)–Poly(ethylene glycol) Blend for Prostate Cancer Treatment

机译：聚ε-己内酯和聚（dl-乳酸-乙醇酸）-聚（乙二醇）共混物的白藜芦醇负载纳米颗粒用于前列腺癌的治疗

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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.
机译：抗增殖和化学预防性植物抗毒素白藜芦醇（RSV）的纳米囊封可能提供保护，防止降解，提高生物利用度，改善细胞内渗透和控制传递。在这项研究中，使用人PCa细胞设计，表征和评估了封装有RSV（nano-RSV）的聚合物纳米颗粒（NPs）作为前列腺癌（PCa）治疗的新原型。纳米系统由聚ε-己内酯（PCL）和聚（d，l-乳酸-乙醇酸）-聚（乙二醇）共轭物（PLGA-PEG-COOH）的生物相容性共混物组成，其制备方法如下：纳米沉淀法，并在形态，粒径和ζ电势，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在PCa细胞系DU-145，PC-3和LNCaP中评估细胞对NP的摄取，并使用MTT分析评估抗增殖功效。封装效率从74％到98％不等，RSV已成功加载到PCL：PLGA-PEG-COOH NP中，其平均直径为150 nm。 NPs能够分别控制pH 6.5和7.4的RSV释放，分别模拟酸性肿瘤微环境和生理条件，在7 h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 h释放约55％的RSV，随后在pH 7.4的5 h内释放总RSV含量。共聚焦荧光显微镜观察显示，NPa被PCa细胞系有效吸收。此外，与游离RSV相比，在所有测试浓度（10 µM至40 µM）下，nano-RSV均显着改善了对所有三种细胞系的细胞毒性，证明了其对雄激素非依赖性DU-145和激素-的敏感性始终如一。敏感的LNCaP细胞。我们的发现支持开发的纳米原型可潜在地用于Pca化学预防/化学治疗的生物活性RSV的受控传递。

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