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姜黄素与白蛋白/紫杉醇纳米颗粒的脂质体共递送用于增强协同抗肿瘤疗效。

Liposomal co-delivery of curcumin and albumin/paclitaxel nanoparticle for enhanced synergistic antitumor efficacy.

作者信息

Ruttala Hima Bindu, Ko Young Tag

机构信息

College of Pharmacy, Gachon University, Incheon 406-799, Republic of Korea.

College of Pharmacy, Gachon University, Incheon 406-799, Republic of Korea.

出版信息

Colloids Surf B Biointerfaces. 2015 Apr 1;128:419-426. doi: 10.1016/j.colsurfb.2015.02.040. Epub 2015 Mar 7.

Abstract

Paclitaxel (PTX) and curcumin (CUR) are potent chemotherapeutic agents used in the treatment of cancer. In the present study, hybrid polymer-lipid nanoparticles co-loaded with PTX and CUR were developed to investigate the therapeutic potential of a combination drug regimen. For this purpose, PTX-loaded albumin nanoparticles (APN) were prepared and encapsulated in PEGylated hybrid liposomes containing CUR (CL-APN) via a thin-film hydration technique. CL-APN was nanosized with a uniform spherical morphology. PTX and CUR release was sustained and occurred in a sequential manner, wherein CUR was expected to downregulate the nuclear factor NF-κB and Akt pathways and increase the therapeutic efficacy of PTX. The ratiometric combination of PTX and CUR was significantly more cytotoxic than the individual drugs. Importantly, dual-drug-loaded nanocarriers exhibited a superior cytotoxic effect than a cocktail combination at a lower dose. CL-APN induced significantly higher early and late apoptosis, induced a stronger G2/M arrest, and significantly increased the subG1 cell population. By combining CUR, an effective NF-κB inhibitor, with PTX, a powerful anticancer drug, in a polymer-lipid hybrid nanoparticle system, we could improve the therapeutic efficacy in cancer treatments. Our results showed that such co-loaded delivery systems could serve as a promising therapeutic approach to improve clinical outcomes against various malignancies.

摘要

紫杉醇(PTX)和姜黄素(CUR)是用于癌症治疗的强效化疗药物。在本研究中,开发了共负载PTX和CUR的杂化聚合物-脂质纳米颗粒,以研究联合用药方案的治疗潜力。为此,制备了负载PTX的白蛋白纳米颗粒(APN),并通过薄膜水化技术将其包裹在含有CUR的聚乙二醇化杂化脂质体(CL-APN)中。CL-APN呈纳米尺寸,具有均匀的球形形态。PTX和CUR的释放是持续的且以顺序方式发生,其中预计CUR会下调核因子NF-κB和Akt信号通路,并提高PTX的治疗效果。PTX和CUR的比例组合比单独的药物具有显著更高的细胞毒性。重要的是,双药负载的纳米载体在较低剂量下比混合组合表现出更强的细胞毒性作用。CL-APN诱导显著更高的早期和晚期凋亡,诱导更强的G2/M期阻滞,并显著增加亚G1期细胞群体。通过在聚合物-脂质杂化纳米颗粒系统中,将有效的NF-κB抑制剂CUR与强效抗癌药物PTX相结合,我们可以提高癌症治疗的疗效。我们的结果表明,这种共负载递送系统可作为一种有前景的治疗方法,以改善针对各种恶性肿瘤的临床结果。

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