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伊立替康和5-氟尿嘧啶共载、透明质酸修饰的层层自组装纳米粒用于靶向胃癌治疗

Irinotecan and 5-fluorouracil-co-loaded, hyaluronic acid-modified layer-by-layer nanoparticles for targeted gastric carcinoma therapy.

作者信息

Gao Zhuanglei, Li Zhaoxia, Yan Jieke, Wang Peilin

机构信息

Department of General Surgery.

Department of Pediatrics.

出版信息

Drug Des Devel Ther. 2017 Sep 5;11:2595-2604. doi: 10.2147/DDDT.S140797. eCollection 2017.

DOI:10.2147/DDDT.S140797
PMID:28919710
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5592948/
Abstract

For targeted gastric carcinoma therapy, hyaluronic acid (HA)-modified layer-by-layer nanoparticles (NPs) are applied for improving anticancer treatment efficacy and reducing toxicity and side effects. The aim of this study was to develop HA-modified NPs for the co-loading of irinotecan (IRN) and 5-fluorouracil (5-FU). A novel polymer-chitosan (CH)-HA hybrid formulation (HA-CH-IRN/5-FU NPs) consisting of poly(d,l-lactide--glycolide) (PLGA) and IRN as the core, CH and 5-FU as a shell on the core and HA as the outmost layer was prepared. Its morphology, average size, zeta potential and drug encapsulation ability were evaluated. Human gastric carcinoma cells (MGC803 cells) and cancer-bearing mice were used for the testing of in vitro cytotoxicity and in vivo antitumor efficiency of NPs. HA-CH-IRN/5-FU NPs displayed enhanced antitumor activity in vitro and in vivo than non-modified NPs, single drug-loaded NPs and drugs solutions. The results demonstrate that HA-CH-IRN/5-FU NPs can achieve impressive antitumor activity and the novel targeted drug delivery system offers a promising strategy for the treatment of gastric cancer.

摘要

为了实现胃癌的靶向治疗，采用透明质酸（HA）修饰的层层组装纳米颗粒（NPs）来提高抗癌治疗效果并降低毒性和副作用。本研究的目的是开发用于共载伊立替康（IRN）和5-氟尿嘧啶（5-FU）的HA修饰纳米颗粒。制备了一种新型聚合物壳聚糖（CH）-HA杂化制剂（HA-CH-IRN/5-FU NPs），其以聚（d，l-丙交酯-乙交酯）（PLGA）和IRN为核心，CH和5-FU包裹在核心上作为壳层，HA作为最外层。对其形态、平均尺寸、zeta电位和药物包封能力进行了评估。用人胃癌细胞（MGC803细胞）和荷瘤小鼠测试纳米颗粒的体外细胞毒性和体内抗肿瘤效果。HA-CH-IRN/5-FU NPs在体外和体内均显示出比未修饰的纳米颗粒、单药负载纳米颗粒和药物溶液更强的抗肿瘤活性。结果表明，HA-CH-IRN/5-FU NPs可实现令人印象深刻的抗肿瘤活性，这种新型靶向给药系统为胃癌治疗提供了一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/df480cee15a6/dddt-11-2595Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/e6e0ff120dec/dddt-11-2595Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/ac55acf963fd/dddt-11-2595Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/0970d0b1efbe/dddt-11-2595Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/00f4b7380173/dddt-11-2595Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/1474187489b5/dddt-11-2595Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/2ff5f066c7ba/dddt-11-2595Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/df480cee15a6/dddt-11-2595Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/e6e0ff120dec/dddt-11-2595Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/ac55acf963fd/dddt-11-2595Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/0970d0b1efbe/dddt-11-2595Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/00f4b7380173/dddt-11-2595Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/1474187489b5/dddt-11-2595Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/2ff5f066c7ba/dddt-11-2595Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de4d/5592948/df480cee15a6/dddt-11-2595Fig7.jpg

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本文引用的文献

[1]
Targeted therapies for gastric cancer: failures and hopes from clinical trials.

Oncotarget. 2017-1-26

[2]
Doxorubicin-loaded poly (lactic-co-glycolic acid) nanoparticles coated with chitosan/alginate by layer by layer technology for antitumor applications.

Int J Nanomedicine. 2017-3-3

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Int J Nanomedicine. 2017-1-31

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Nanomedicine (Lond). 2017-2-9

[9]
In vivo evaluation of a self-nanoemulsifying drug delivery system for curcumin.

Biomed Pharmacother. 2017-4

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Thermosensitive hydrogel based on chitosan and its derivatives containing medicated nanoparticles for transcorneal administration of 5-fluorouracil.

Int J Nanomedicine. 2017-1-16

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