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含紫杉醇的双功能脂质体治疗肺癌的疗效

Efficacy of dual-functional liposomes containing paclitaxel for treatment of lung cancer.

作者信息

Wang Rong-Hua, Cao Hong-Mei, Tian Zhi-Ju, Jin Bo, Wang Qing, Ma Hong, Wu Jing

机构信息

Department of Cardiothoracic Surgery, People's Hospital of Zhangqiu, Zhangqiu, Shandong 250200, P.R. China.

Pharmacy Intravenous Admixture Services, People's Hospital of Zhangqiu, Zhangqiu, Shandong 250200, P.R. China.

出版信息

Oncol Rep. 2015 Feb;33(2):783-91. doi: 10.3892/or.2014.3644. Epub 2014 Dec 2.


DOI:10.3892/or.2014.3644
PMID:25482610
Abstract

This study was mainly focused on the development of a dual-ligand liposomal delivery system for targeting the delivery of paclitaxel (PTX) to lung cancer. The specific ligand peptide HAIYPRH (T7) and the cationic cell-penetrating peptide TAT were connected with phospholipid via a polyethylene glycol (PEG) spacer to prepare the dual-ligand liposomes (T7/TAT-LP-PTX). Physicochemical characterizations of T7/TAT-LP-PTX, such as particle size, ζ potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. In the cellular uptake study, the T7/TAT-LP endocytosed by the A549 cells was 2.26-, 3.48- and 8.56-fold higher than TAT-LP, T7-LP and LP, respectively. The IC50 values of TAT-LP-PTX, T7-LP-PTX and LP-PTX were much higher than those of T7/TAT-LP-PTX, respectively. The homing specificity of T7/TAT-LP was evaluated on the tumor spheroids, which revealed that T7/TAT-LP was more efficaciously internalized in tumor cells than TAT-LP, T7-LP and LP, respectively. Compared to LP, TAT-LP and T7-LP, T7/TAT-LP showed the strongest cell uptake property, and the highest accumulation ability in tumor spheroids in vitro. In the in vivo study, the T7/TAT-LP-PTX exhibited the best inhibitory effect of tumor growth for A549-bearing mice. Collectively, these results suggested that T7/TAT-LP-PTX is a promising drug delivery system for the treatment of lung cancer.

摘要

本研究主要聚焦于开发一种双配体脂质体递送系统,用于将紫杉醇(PTX)靶向递送至肺癌细胞。将特异性配体肽HAIYPRH(T7)和阳离子细胞穿透肽TAT通过聚乙二醇(PEG)间隔物与磷脂连接,制备双配体脂质体(T7/TAT-LP-PTX)。还评估了T7/TAT-LP-PTX的物理化学特性,如粒径、ζ电位、形态、包封率和体外PTX释放。在细胞摄取研究中,A549细胞内吞的T7/TAT-LP分别比TAT-LP、T7-LP和LP高2.26倍、3.48倍和8.56倍。TAT-LP-PTX、T7-LP-PTX和LP-PTX的IC50值分别远高于T7/TAT-LP-PTX。在肿瘤球体上评估了T7/TAT-LP的归巢特异性,结果显示T7/TAT-LP分别比TAT-LP、T7-LP和LP更有效地内化于肿瘤细胞中。与LP、TAT-LP和T7-LP相比,T7/TAT-LP表现出最强的细胞摄取特性和体外肿瘤球体中最高的积累能力。在体内研究中,T7/TAT-LP-PTX对荷A549小鼠的肿瘤生长表现出最佳抑制作用。总体而言,这些结果表明T7/TAT-LP-PTX是一种有前景的治疗肺癌的药物递送系统。

相似文献

[1]
Efficacy of dual-functional liposomes containing paclitaxel for treatment of lung cancer.

Oncol Rep. 2015-2

[2]
Tumor-targeted paclitaxel delivery and enhanced penetration using TAT-decorated liposomes comprising redox-responsive poly(ethylene glycol).

J Pharm Sci. 2015-3

[3]
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Int J Clin Exp Pathol. 2015-1-1

[4]
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Drug Deliv. 2015-6-3

[5]
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Curr Pharm Biotechnol. 2016

[6]
[Preparation of cell penetrating peptide TAT and cleavable PEGco-modified liposomes loaded with paclitaxel and its in vitro apoptosis assay].

Yao Xue Xue Bao. 2014-7

[7]
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Int J Pharm. 2013-7-10

[8]
[Preparation and evaluation of RGD and TAT co-modified paclitaxel loaded liposome].

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[9]
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J Control Release. 2015-9-12

[10]
Improved Antitumor Activity of Novel Redox-Responsive Paclitaxel-Encapsulated Liposomes Based on Disulfide Phosphatidylcholine.

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引用本文的文献

[1]
Advances in Delivery of Chemotherapeutic Agents for Cancer Treatment.

AAPS PharmSciTech. 2021-12-14

[2]
Efficacy and Safety of Image-Guided Intensity-Modulated Radiation Therapy and Volumetric Modulated Arc Therapy Combined with Paclitaxel Liposomes and Cisplatin for Locally Advanced Stage IIB-IIIB Cervical Cancer: A Retrospective Study at a Single Center.

Med Sci Monit. 2020-12-9

[3]
Nano targeted Therapies Made of Lipids and Polymers have Promising Strategy for the Treatment of Lung Cancer.

Materials (Basel). 2020-11-27

[4]
Liposomal paclitaxel versus docetaxel in induction chemotherapy using Taxanes, cisplatin and 5-fluorouracil for locally advanced nasopharyngeal carcinoma.

BMC Cancer. 2018-12-20

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