Targeted Delivery of DNA Topoisomerase Inhibitor SN38 to Intracranial Tumors of Glioblastoma Using Sub-5 Ultrafine Iron Oxide Nanoparticles.
Targeted Delivery of DNA Topoisomerase Inhibitor SN38 to Intracranial Tumors of Glioblastoma Using Sub-5 Ultrafine Iron Oxide Nanoparticles.
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纳米氧化铁靶向治疗胶质母细胞瘤的研究
DOI：
10.1002/adhm.202102816
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发表时间：
2022-07
影响因子：
10
通讯作者：
Mao, Hui
中科院分区：
文献类型：
--
作者：
Li, Yuancheng;Xie, Manman;Jones, Joshua B.;Zhang, Zhaobin;Wang, Zi;Dang, Tu;Wang, Xinyu;Lipowska, Malgorzata;Mao, Hui
有效地递送用于治疗脑肿瘤的治疗剂受到脑中的物理和生物屏障的阻碍。即使在胶质母细胞瘤（GBM）中观察到血脑屏障受损和高度血管生成的血肿瘤屏障，大多数药物，包括基于纳米材料的制剂，也很难到达颅内肿瘤。本工作研究了核直径为3.5 nm的亚5 nm超细氧化铁纳米颗粒（uIONP）作为载体，用于递送DNA拓扑异构酶抑制剂7-乙基-10-羟基喜树碱（SN 38）治疗GBM。给定较高的表面积与体积比，uIONP显示出比具有10或20 nm的核尺寸的那些高1或3倍的SN 38负载效率（48.3 ± 6.1%，SN 38/Fe，wt%）。包封在包衣聚合物中的SN 38表现出pH敏感性释放，在pH 7.4下48小时内<10%，但在pH 5下为86%，因此被UDP-葡糖醛酸基转移酶1A 1保护而不转化为无活性的葡糖苷酸。结合αvβ3-整合素靶向的cyclo（Arg-Gly-Asp-D-Phe-Cys）（RGD）作为配体，RGD-uIONP/SN 38表现出对αvβ3整合素过表达的U87 MG GBM细胞的靶向细胞毒性，IC 50为30.9 ± 2.2 nM。使用GBM的原位小鼠模型的体内研究揭示了11.5%注射的RGD-uIONP/SN 38（10 mg Fe/kg）的肿瘤特异性递送，与用单独的SN 38处理的那些相比，小鼠中的存活显著延长~ 41%（p < 0.001）。报道了以直径为3.5nm的超细氧化铁纳米粒（uIONP）为载体，将难溶性化疗药物7-乙基-10-羟基喜树碱（SN 38）递送至颅内肿瘤。以环肽RGD作为靶向肿瘤整合素的配体，RGD-uIONP/SN 38对U87 MG胶质母细胞瘤细胞具有肿瘤特异性细胞毒性，延长胶质母细胞瘤小鼠的存活。
Effectively delivering therapeutics for treating brain tumors has been hindered by the physical and biological barriers in the brain. Even with the compromised blood-brain barrier and highly angiogenic blood-tumor barrier seen in glioblastoma (GBM), most drugs, including nanomaterial-based formulations, hardly reach intracranial tumors. This work investigated sub-5 nm ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier for delivering DNA topoisomerase inhibitor 7-ethyl-10-hydroxyl camptothecin (SN38) to treat GBM. Given a higher surface-to-volume ratio, uIONP shows 1 or 3-folds higher SN38 loading efficiency (48.3 ± 6.1%, SN38/Fe, wt%) than those with core sizes of 10 or 20 nm. SN38 encapsulated in the coating polymer exhibits pH sensitive release with <10% over 48 hours at pH 7.4, but 86% at pH 5, thus being protected from converting to inactive glucuronide by UDP-glucuronosyltransferase 1A1. Conjugating αvβ3-integrin-targeted cyclo(Arg-Gly-Asp-D-Phe-Cys) (RGD) as ligands, RGD-uIONP/SN38 demonstrated targeted cytotoxicity to αvβ3 integrin overexpressed U87MG GBM cells with a IC50 of 30.9 ± 2.2 nM. The in vivo study using an orthotopic mouse model of GBM reveals tumor-specific delivery of 11.5% injected RGD-uIONP/SN38 (10 mg Fe/kg), significantly prolonging the survival in mice by ~41%, comparing to those treated with SN38 alone (p < 0.001). Using ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier to deliver insoluble chemotherapy agent, 7-ethyl-10-hydroxyl camptothecin (SN38), to intracranial tumors is reported. With cyclic peptide RGD as the ligand targeting the tumor integrin, RGD-uIONP/SN38 exerts tumor specific cytotoxicity to U87MG glioblastoma cells, prolonging survival of mice with glioblastoma.
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DOI：
10.4049/jimmunol.1700128
发表时间：
2017-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brilha S;Wysoczanski R;Whittington AM;Friedland JS;Porter JC
通讯作者：
Porter JC
嵌段共聚物纳米颗粒的选择性溶胀：尺寸、纳米结构和组成
影响因子：
5.5
作者：
Fan, Hailong;Jin, Zhaoxia
通讯作者：
Jin, Zhaoxia
DOI：
10.1089/jamp.2013.1117
发表时间：
2015-02-01
影响因子：
3.4
作者：
Graczyk, Halshka;Bryan, Louise C.;Riediker, Michael
通讯作者：
Riediker, Michael
DOI：
10.1073/pnas.0913290107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Fujiwara, Ryoichi;Nguyen, Nghia;Tukey, Robert H.
通讯作者：
Tukey, Robert H.
影响因子：
4.5
作者：
de Man FM;Goey AKL;van Schaik RHN;Mathijssen RHJ;Bins S
通讯作者：
Bins S