由cRGD共轭βCD-PAMAM-PEG形成的多功能药物纳米载体用于靶向癌症治疗。
Multifunctional drug nanocarriers formed by cRGD-conjugated βCD-PAMAM-PEG for targeted cancer therapy.
作者信息
Saraswathy Manju, Knight Gavin T, Pilla Srikanth, Ashton Randolph S, Gong Shaoqin
机构信息
Department of Biomedical Engineering and Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA.
出版信息
Colloids Surf B Biointerfaces. 2015 Feb 1;126:590-597. doi: 10.1016/j.colsurfb.2014.12.042. Epub 2015 Jan 3.
Polyamidoamine (PAMAM) dendrimer was conjugated with both carboxymethyl-β-cyclodextrin (βCD) and poly(ethylene glycol) (PEG). Cyclic RGD peptide, used as a tumor targeting ligand, was then selectively conjugated onto the distal ends of the PEG arms. The resulting βCD-PAMAM-PEG-cRGD polymer was able to form stable and uniform nanoparticles (NPs) in aqueous solution. Doxorubicin (Dox), a model hydrophobic anticancer drug, was effectively encapsulated in the NPs via an inclusion complex formed between the drug and βCD. The Dox loading level was 16.8 wt%. The cellular uptake of cRGD-conjugated Dox-loaded NPs in the U87MG cell line was much higher than that of non-targeted NPs. Furthermore, the anti-proliferative effect of the cRGD-conjugated NPs was superior to that of free drug and non-targeted NPs. These results suggest that NPs formed by βCD-PAMAM-PEG-cRGD with a high drug payload may significantly improve the anticancer efficacy by tumor-targeted delivery and enhanced cellular uptake.
聚酰胺-胺（PAMAM）树枝状大分子与羧甲基-β-环糊精（βCD）和聚乙二醇（PEG）进行了共轭。用作肿瘤靶向配体的环状RGD肽随后被选择性地共轭到PEG臂的末端。所得的βCD-PAMAM-PEG-cRGD聚合物能够在水溶液中形成稳定且均匀的纳米颗粒（NPs）。阿霉素（Dox）是一种典型的疏水性抗癌药物，通过药物与βCD之间形成的包合物有效地包裹在NPs中。阿霉素的负载量为16.8 wt%。cRGD共轭的载药NPs在U87MG细胞系中的细胞摄取量远高于非靶向NPs。此外，cRGD共轭NPs的抗增殖作用优于游离药物和非靶向NPs。这些结果表明，由βCD-PAMAM-PEG-cRGD形成的具有高药物负载量的NPs可通过肿瘤靶向递送和增强细胞摄取显著提高抗癌疗效。
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