A hematoporphyrin-based delivery system for drug resistance reversal and tumor ablation
A hematoporphyrin-based delivery system for drug resistance reversal and tumor ablation
复制标题
基于血卟啉的递送系统用于耐药性逆转和肿瘤消融
DOI：
10.1016/j.biomaterials.2013.12.004
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发表时间：
2014-03-01
期刊：
影响因子：
14
通讯作者：
Zhang, Ning
中科院分区：
文献类型：
--
作者：
Ren, Yu;Wang, Ruirui;Zhang, Ning
基于纳米技术的给药系统已得到广泛的研究，但只有少数几种药物可用于临床。血卟啉（HP）是红细胞中的主要分子，已广泛应用于光动力学治疗（PDT）。本研究设计了聚乙二醇（PEG）修饰的血卟啉（HPP）纳米粒系统负载阿霉素（HPPD），以实现化疗和PDT的协同效应。在此，我们提出HPPD在35 +/- 2 nm处形成窄分散的纳米颗粒，在pH 5.8下沿着激光辐射产生增强的药物释放。这种HPPD和放射的联合治疗促进了药物渗透到细胞核，从而减少了IC 50值的12倍下降，并促进了耐药乳腺癌细胞的凋亡。值得注意的是，在细胞水平和动物模型中，HPP几乎没有检测到毒性。活体动物成像显示，HPPD在小鼠和绒猴模型中均表现出超高的肿瘤摄取。引人注目的是，静脉内施用HPPD和对肿瘤的放射实现了有效的肿瘤消融，而不诱导心肌损伤。我们在这里报告的生物分子，HP为基础的纳米粒子系统，它可以协同产生化疗和PDT的发展。(C)2013爱思唯尔有限公司保留所有权利。
Nanotechnology-based drug delivery systems have been intensively investigated, while only a few of them can be used for clinic application. Hematoporphyrin (HP), a major molecule in erythrocyte, has been widely used in photodynamic therapy (PDT). In the present study, polyethylene glycol (PEG) modified hematoporphyrin (HPP)-based nanoparticle system was designed to load doxorubicin (HPPD), in achieving a synergistic effect of chemotherapy and PDT. Herein we presented that HPPD formed narrowly dispersed nanoparticles at 35 +/- 2 nm, yielding an enhanced drug release at pH5.8 along with laser radiation. This combined treatment with HPPD and radiation facilitated drug penetration to the nucleus thereby reducing 12-fold decrease in IC50 value and promoting apoptosis in drug-resistant breast cancer cells. Notably, little toxicity was detected with HPP at the cellular level and in animal models. Live animal imaging revealed that HPPD performed ultra high tumor uptake in both mice and marmoset models. Strikingly, intravenous administration of HPPD and radiation on the tumor achieved efficient tumor ablation, without inducing myocardial injury. We report here the development of a biomolecule, HP-based nanoparticle system, which can synergistically yield chemotherapy and PDT. (C) 2013 Elsevier Ltd. All rights reserved.