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自组装还原型白蛋白和乙二醇壳聚糖纳米粒用于紫杉醇递送。

Self-Assembled Reduced Albumin and Glycol Chitosan Nanoparticles for Paclitaxel Delivery.

机构信息

Department of Applied Chemistry, Graduate School of Engineering , Kyushu University , Motooka 744 , Nishi-ku, Fukuoka 819-0395 , Japan.

Division of Biotechnology, Center for Future Chemistry , Kyushu University , Motooka 744 , Nishi-ku, Fukuoka 819-0395 , Japan.

出版信息

Langmuir. 2019 Feb 19;35(7):2610-2618. doi: 10.1021/acs.langmuir.8b02809. Epub 2019 Feb 6.

Abstract

Cancer continues to pose health problems for people all over the world. Nanoparticles (NPs) have emerged as a promising platform for effective cancer chemotherapy. NPs formed by the assembly of proteins and chitosan (CH) through noncovalent interactions are attracting a great deal of interest. However, the poor water solubility of CH and low stability of this kind of NP limit its practical application. Herein, the formation of reduced bovine serum albumin (rBSA) and glycol chitosan (GC) nanoparticles (rBG-NPs) stabilized by hydrophobic interactions and disulfide bonds was demonstrated for paclitaxel (PTX) delivery. The effects of the rBSA:GC mass ratio and pH on the particle size, polydispersity index (PDI), number of particles, and surface charge were evaluated. The formation mechanism and stability of the NPs were determined by compositional analysis and dynamic light scattering. Hydrophobic and electrostatic interactions were the driving forces for the formation of the rBG-NPs, and the NPs were stable under physiological conditions. PTX was successfully encapsulated into rBG-NPs with a high encapsulation efficiency (∼90%). PTX-loaded rBG-NPs had a particle size of ∼400 nm with a low PDI (0.2) and positive charge. rBG-NPs could be internalized by HeLa cells, possibly via endocytosis. An in vitro cytotoxicity study revealed that PTX-loaded rBG-NPs had anticancer activity that was lower than that of a Taxol-like formulation at 24 h but had similar activity at 48 h, possibly because of the slow release of PTX into the cells. Our study suggests that rBG-NPs could be used as a potential nanocarrier for hydrophobic drugs.

摘要

癌症仍然是全世界人民面临的健康问题。纳米颗粒(NPs)已成为有效癌症化疗的有前途的平台。通过非共价相互作用由蛋白质和壳聚糖(CH)组装而成的 NPs 引起了极大的兴趣。然而,CH 的低水溶性和这种 NP 的低稳定性限制了其实际应用。在此,通过疏水性相互作用和二硫键稳定,展示了还原牛血清白蛋白(rBSA)和乙二醇壳聚糖(GC)纳米颗粒(rBG-NPs)的形成用于紫杉醇(PTX)的递送。评估了 rBSA:GC 质量比和 pH 值对粒径、多分散指数(PDI)、颗粒数和表面电荷的影响。通过组成分析和动态光散射确定了 NPs 的形成机制和稳定性。疏水性和静电相互作用是形成 rBG-NPs 的驱动力,并且 NPs 在生理条件下稳定。PTX 成功地包封到 rBG-NPs 中,包封效率约为 90%。载有 PTX 的 rBG-NPs 的粒径约为 400nm,PDI 低(0.2)且带正电荷。rBG-NPs 可以被 HeLa 细胞内化,可能是通过内吞作用。体外细胞毒性研究表明,载有 PTX 的 rBG-NPs 在 24 小时时的抗癌活性低于 Taxol 样制剂,但在 48 小时时具有相似的活性,这可能是因为 PTX 缓慢释放到细胞中。我们的研究表明,rBG-NPs 可用作疏水性药物的潜在纳米载体。

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