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首页> 外文期刊>Biomaterials >A hematoporphyrin-based delivery system for drug resistance reversal and tumor ablation
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A hematoporphyrin-based delivery system for drug resistance reversal and tumor ablation

机译：基于血卟啉的药物传递系统，可用于耐药性逆转和肿瘤消融

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摘要

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±2nm, 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.
机译：基于纳米技术的药物输送系统已得到深入研究，而其中只有少数可用于临床。血卟啉（HP）是红细胞中的主要分子，已被广泛用于光动力疗法（PDT）中。在本研究中，基于聚乙二醇（PEG）修饰的血卟啉（HPP）的纳米粒子系统被设计为加载阿霉素（HPPD），以实现化学疗法和PDT的协同作用。在本文中，我们介绍了HPPD在35±2nm处形成了窄分散的纳米颗粒，在pH5.8和激光辐射的作用下，药物释放增强。 HPPD和辐射的这种联合治疗促进了药物向核的渗透，从而使IC50值降低了12倍，并促进了耐药性乳腺癌细胞的凋亡。值得注意的是，在细胞水平和动物模型中，HPP几乎未检测到毒性。活体动物成像显示，HPPD在小鼠和mar猴模型中均具有超高的肿瘤吸收率。引人注目的是，在肿瘤上静脉内注射HPPD和放射线可实现有效的肿瘤消融，而不会引起心肌损伤。我们在这里报告了一种基于HP的生物分子纳米系统的开发，该系统可以协同产生化学疗法和PDT。

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