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载盐酸伊达比星的甲氧基聚乙二醇-聚（L-丙交酯-共-乙交酯）纳米粒用于增强细胞摄取并提高抗白血病活性。

Idarubicin-loaded methoxy poly(ethylene glycol)--poly(l-lactide-co-glycolide) nanoparticles for enhancing cellular uptake and promoting antileukemia activity.

机构信息

Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Wenzhou, Zhejiang 325000, China.

Wenzhou Institute of Biomaterials and Engineering, CNITECH, CAS, Wenzhou, Zhejiang 325000, China.

出版信息

Int J Nanomedicine. 2019 Jan 11;14:543-556. doi: 10.2147/IJN.S190027. eCollection 2019.

DOI:10.2147/IJN.S190027
PMID:30666113
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6333394/
Abstract

PURPOSE

Nanoparticle (NP)-based drug delivery approaches have tremendous potential for enhancing treatment efficacy and decreasing doses of chemotherapeutics. Idarubicin (IDA) is one of the most common chemotherapeutic drugs used in the treatment of acute myeloid leukemia (AML). However, severe side effects and drug resistance markedly limit the application of IDA.

METHODS

In this study, we encapsulated IDA in polymeric NPs and validated their antileukemia activity in vitro and in vivo.

RESULTS

NPs with an average diameter of 84 nm was assembled from a methoxy poly(ethylene glycol)--poly(l-lactide-co-glycolide) (mPEG-PLGA). After loading of IDA, IDA-loaded mPEG-PLGA NPs (IDA/mPEG-PLGA NPs) were formed. The in vitro release data showed that the IDA/mPEG-PLGA NPs have excellent sustained release property. IDA/mPEG-PLGA NPs had exhibited the lower IC than pure IDA. Moreover, IDA/mPEG-PLGA NPs in the same concentration substantially induced apoptosis than did pure IDA. Most importantly, IDA/MPEG-PLGA NPs significantly decreased the infiltration of leukemia blasts and improved the overall survival of MLL-AF9-induced murine leukemia compared with free IDA. However, the blank NPs were nontoxic to normal cultured cells in vitro, suggesting that NPs were the safe carrier.

CONCLUSION

Our data suggest that IDA/mPEG-PLGA NPs might be a suitable carrier to encapsulate IDA. Low dose of IDA/mPEG-PLGA NPs can be used as a conventional dosage for antileukemia therapy to reduce side effect and improve survival.

摘要

目的

基于纳米粒子（NP）的药物递送方法具有增强治疗效果和降低化疗药物剂量的巨大潜力。柔红霉素（IDA）是治疗急性髓系白血病（AML）中最常用的化疗药物之一。然而，严重的副作用和耐药性显著限制了 IDA 的应用。

方法

在这项研究中，我们将 IDA 封装在聚合物 NP 中，并在体外和体内验证了它们的抗白血病活性。

结果

由甲氧基聚（乙二醇）-聚（L-丙交酯-co-乙交酯）（mPEG-PLGA）组装而成的平均直径为 84nm 的 NPs。负载 IDA 后，形成了载有 IDA 的 mPEG-PLGA NPs（IDA/mPEG-PLGA NPs）。体外释放数据表明，IDA/mPEG-PLGA NPs 具有优异的持续释放性能。IDA/mPEG-PLGA NPs 的 IC 低于纯 IDA。此外，与纯 IDA 相比，相同浓度的 IDA/mPEG-PLGA NPs 能显著诱导细胞凋亡。最重要的是，与游离 IDA 相比，IDA/mPEG-PLGA NPs 显著减少了白血病母细胞的浸润，提高了 MLL-AF9 诱导的小鼠白血病的总生存率。然而，空白 NPs 在体外对正常培养的细胞没有毒性，这表明 NPs 是安全的载体。

结论

我们的数据表明，IDA/mPEG-PLGA NPs 可能是一种合适的载体来封装 IDA。低剂量的 IDA/mPEG-PLGA NPs 可作为常规剂量用于抗白血病治疗，以减少副作用并提高生存率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/489a736ac501/ijn-14-543Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/0f77f4cef787/ijn-14-543Fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/40c3baf6b4fb/ijn-14-543Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/3f2d74b0b218/ijn-14-543Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/489a736ac501/ijn-14-543Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/0f77f4cef787/ijn-14-543Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/0cf5c34e3842/ijn-14-543Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/4024af347b3f/ijn-14-543Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/d135978e7cf9/ijn-14-543Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/296e9876137e/ijn-14-543Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/40c3baf6b4fb/ijn-14-543Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/3f2d74b0b218/ijn-14-543Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec1f/6333394/489a736ac501/ijn-14-543Fig8.jpg

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