Theranostic Hyaluronic Acid-Iron Micellar Nanoparticles for Magnetic-Field-Enhanced in vivo Cancer Chemotherapy.
Theranostic Hyaluronic Acid-Iron Micellar Nanoparticles for Magnetic-Field-Enhanced in vivo Cancer Chemotherapy.
复制标题
用于磁场增强体内癌症化疗的治疗诊断透明质酸-铁胶束纳米颗粒。
DOI：
10.1002/cmdc.201700515
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发表时间：
2018
期刊：
影响因子：
3.4
通讯作者：
Zhu Lei
中科院分区：
文献类型：
--
作者：
Wang Guohao;Gao Shi;Tian Rui;Miller-Kleinhenz Jasmine;Qin Zainen;Liu Tianji;Li Lu;Zhang Fan;Ma Qingjie;Zhu Lei
使用纳米材料递送治疗性癌症药剂最近引起了广泛关注。尽管化疗药物取得了令人鼓舞的进展，但肿瘤治疗反应仍不令人满意。为了解决这个问题，我们构建了一个新的胶束纳米复合物共价结合透明质酸（HA）与氧化铁纳米粒子（IONP）。当将外部磁场施加到肿瘤区域时，由于强IONP磁性，HA-IONP特异性地在肿瘤中积累。此外，HA显示结合簇决定簇44（CD 44），其在肿瘤细胞上过表达。 通过组合的磁性、CD 44和增强的渗透性保留（EPR）靶向，HA-IONP向肿瘤的有效递送预计将提高癌症治疗效率。将化疗药物高喜树碱（HCPT）包裹后，在体外和体内研究了HA-IONP/HCPT（HIH）的治疗诊断效力。 磁共振成像（MRI）观察到当使用外磁场时，HIH的肿瘤归巢行为得到改善。此外，HIH显示出显著的肿瘤消融效率，在3 mg kg− 1静脉给药（相当于游离HCPT的剂量）后具有磁靶向作用，治疗后肿瘤几乎消失。 未见明显的全身毒性反应。这种优异的生物相容性和肿瘤靶向性表明HIH是一种具有巨大转化潜力的有前途的治疗诊断纳米复合物。HA-IONP平台的应用也可以扩展到其他疏水性化疗药物或光疗剂的递送。
The delivery of therapeutic cancer agents using nanomaterials has recently attracted much attention. Although encouraging progress with chemotherapeutics has been made, tumor treatment response remains unsatisfactory. To address this concern, we constructed a new micellar nanocomplex by covalently conjugating hyaluronic acid (HA) with an iron oxide nanoparticle (IONP). When an external magnetic field was applied to the tumor area, HA–IONP specifically accumulated in the tumor, due to the strong IONP magnetism. In addition, HA was shown to bind to cluster determinant 44 (CD44), which is overexpressed on tumor cells. With combined magnetic, CD44, and enhanced permeability retention (EPR) targeting, the efficient delivery of HA–IONP to the tumor is expected to enhance cancer treatment efficiency. After encapsulation of the chemotherapy drug homocamptothecin (HCPT), the theranostic potency of HA–IONP/HCPT (HIH) was investigated both in vitro and in vivo. The improved tumor homing behavior of HIH was observed by magnetic resonance imaging (MRI) when an external magnetic field was used. Moreover, HIH showed remarkable tumor ablation efficiency, with magnetic targeting after 3 mg kg−1intravenous administration (equivalent dose of free HCPT), and the tumors almost disappeared after treatment. No obvious systemic toxicity was detected. This excellent biocompatibility and tumor targetability suggests that HIH is a promising theranostic nanocomplex with great translational potency. Application of the HA–IONP platform could also be extended to delivery of other hydrophobic chemotherapy drugs or phototherapy agents.