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用于肝癌治疗的基于二氧化硅纳米颗粒的双响应纳米前药系统。

Silica nanoparticle-based dual-responsive nanoprodrug system for liver cancer therapy.

作者信息

Xia Qing, Li Lina, Zhao Liran

机构信息

Department of Digestive Internal Medicine, Daqing LongNan Hospital, Daqing, Heilongjiang 163453, P.R. China.

出版信息

Exp Ther Med. 2017 Sep;14(3):2071-2077. doi: 10.3892/etm.2017.4768. Epub 2017 Jul 11.

DOI:10.3892/etm.2017.4768
PMID:28962126
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5609098/
Abstract

A thiol-terminated polyethyleneglycol (PEG)-paclitaxel (PTX) conjugate was synthesized and utilized to construct a novel drug delivery system with thiol-functionalized silica nanoparticles (SLNs) to improve the overall performance of PTX in liver cancer therapy. Drug loading was performed by coating the PTX conjugate on the surface of SLNs. The PTX-PEG/SLNs showed a binary responsive drug release behavior to esterase as well as high concentrations of glutathione. The synergic effects of these cancer cell-specific factors on the release characteristics of PTX-PEG/SLNs resulted in a significantly (P<0.01) elevated anti-cancer efficiency. This included prolonged circulation and passive tumor-targeting properties due to surface modification of PEG and targeted release of PTX inside tumor cells, which resulted in increased anti-cancer efficiency. Improving the properties of PTX-PEG/SLNs not only significantly (P<0.01) enhanced its therapeutic efficacy in a murine liver cancer model, but rendered these drug-conjugated SLNs a promising nanoprodrug system for potential use as clinical cancer therapeutics.

摘要

合成了一种巯基封端的聚乙二醇（PEG）-紫杉醇（PTX）共轭物，并将其用于构建一种新型药物递送系统，该系统由巯基功能化的二氧化硅纳米颗粒（SLNs）组成，以提高PTX在肝癌治疗中的整体性能。通过将PTX共轭物包被在SLNs表面来进行药物负载。PTX-PEG/SLNs对酯酶以及高浓度谷胱甘肽表现出二元响应药物释放行为。这些癌细胞特异性因子对PTX-PEG/SLNs释放特性的协同作用导致抗癌效率显著（P<0.01）提高。这包括由于PEG的表面修饰而延长的循环时间和被动肿瘤靶向特性，以及PTX在肿瘤细胞内的靶向释放，从而提高了抗癌效率。改善PTX-PEG/SLNs的性能不仅在小鼠肝癌模型中显著（P<0.01）增强了其治疗效果，还使这些药物共轭的SLNs成为一种有前景的纳米前药系统，有望用作临床癌症治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c234/5609098/d961cb616f84/etm-14-03-2071-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c234/5609098/96e6bf4ac093/etm-14-03-2071-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c234/5609098/2df67503a5fc/etm-14-03-2071-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c234/5609098/9aa9de410ce3/etm-14-03-2071-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c234/5609098/c00d49088e0e/etm-14-03-2071-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c234/5609098/d961cb616f84/etm-14-03-2071-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c234/5609098/96e6bf4ac093/etm-14-03-2071-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c234/5609098/2df67503a5fc/etm-14-03-2071-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c234/5609098/9aa9de410ce3/etm-14-03-2071-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c234/5609098/c00d49088e0e/etm-14-03-2071-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c234/5609098/d961cb616f84/etm-14-03-2071-g04.jpg

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