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利用小鼠血管内皮瘤模型开发用于婴儿血管瘤的纳米颗粒递送高效治疗方法。

Developing a Nanoparticle-Delivered High-Efficacy Treatment for Infantile Hemangiomas Using a Mouse Hemangioendothelioma Model.

作者信息

Orbay Hakan, Li Yuanpei, Xiao Wenwu, Cherry Simon R, Lam Kit, Sahar David E

机构信息

Sacramento and Davis, Calif.

From the Department of Surgery, Division of Plastic Surgery, and the Department of Biochemistry and Molecular Medicine, University of California-Davis Medical Center; and the Department of Biomedical Engineering, University of California-Davis.

出版信息

Plast Reconstr Surg. 2016 Aug;138(2):410-417. doi: 10.1097/PRS.0000000000002403.

DOI:10.1097/PRS.0000000000002403
PMID:27465164
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5472049/
Abstract

BACKGROUND

Current treatments for infantile hemangiomas have unpredictable outcomes. The authors' aim was to develop a nanoporphyrin-delivered, high-efficacy treatment for infantile hemangiomas using a mouse hemangioendothelioma model.

METHODS

The authors injected mouse hemangioendothelioma cells intradermally to axillary regions of 5-week-old, female, nude mice (n = 19) to induce hemangioendothelioma growth. They documented nanoporphyrin accumulation in hemangioendotheliomas using positron emission tomography. For the treatment study, the authors randomized hemangioendothelioma-bearing nude mice (n = 9) into three groups (n = 3 each). Group I received only saline injections. Group II received only laser treatment after saline injection, and group III received laser treatment after nanoporphyrin injection through the tail vein. The authors followed up the treatment response with digital caliper measurements.

RESULTS

Hemangioendotheliomas started to grow approximately 1 week after inoculation and resembled infantile hemangiomas histologically. Nanoporphyrin uptake in hemangioendotheliomas was 19.7 ± 2.2, 16.7 ± 2.02, 8.4 ± 0.3, and 4.9 ± 0.6 percent injected dose per gram of tissue at 3, 6, 24, and 48 hours after injection, respectively. Nanoporphyrin uptake was significantly higher than in blood at 24 and 48 hours after injection (p < 0.05). Results of ex vivo biodistribution study were consistent with positron emission tomographic imaging. Hemangioendotheliomas in group III started to regress 1 day after the treatment and disappeared totally by day 21. The difference between tumor volumes in group III and other groups was significant on days 17 and 21 (p < 0.05).

CONCLUSIONS

Nanoporphyrin accumulated in hemangioendotheliomas at high concentrations, enabling a high-efficacy photodynamic therapy. Given the similarities between hemangioendotheliomas and infantile hemangiomas, this treatment potentially can be a high-efficacy treatment for infantile hemangiomas.

摘要

背景

目前针对婴儿血管瘤的治疗效果难以预测。作者的目的是利用小鼠血管内皮瘤模型开发一种纳米卟啉递送的高效婴儿血管瘤治疗方法。

方法

作者将小鼠血管内皮瘤细胞皮内注射到5周龄雌性裸鼠(n = 19)的腋窝区域,以诱导血管内皮瘤生长。他们使用正电子发射断层扫描记录纳米卟啉在血管内皮瘤中的蓄积情况。在治疗研究中,作者将荷血管内皮瘤的裸鼠(n = 9)随机分为三组(每组n = 3)。第一组仅接受生理盐水注射。第二组在注射生理盐水后仅接受激光治疗,第三组在通过尾静脉注射纳米卟啉后接受激光治疗。作者用数字卡尺测量随访治疗反应。

结果

血管内皮瘤在接种后约1周开始生长,组织学上类似于婴儿血管瘤。注射后3、6、24和48小时,血管内皮瘤中纳米卟啉的摄取量分别为每克组织19.7±2.2、16.7±2.02、8.4±0.3和4.9±0.6注射剂量百分比。注射后24和48小时,纳米卟啉的摄取量显著高于血液中的摄取量(p < 0.05)。体外生物分布研究结果与正电子发射断层扫描成像一致。第三组的血管内皮瘤在治疗后1天开始消退,到第21天完全消失。在第17天和第21天,第三组与其他组的肿瘤体积差异显著(p < 0.05)。

结论

纳米卟啉在血管内皮瘤中高浓度蓄积,可实现高效光动力治疗。鉴于血管内皮瘤与婴儿血管瘤的相似性,这种治疗方法可能成为婴儿血管瘤的高效治疗方法。

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