State Key Laboratory for Modification of Chemical Fiber and Polymer Materials, International Joint Laboratory for Advanced Fiber and Low-dimension Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201600, People's Republic of China.
Department of Radiology, Shanghai Songjiang District Central Hospital, Shanghai 201600, People's Republic of China.
Theranostics. 2020 Feb 3;10(6):2791-2802. doi: 10.7150/thno.42906. eCollection 2020.
Development of unique theranostic nanoplatforms for tumor imaging and therapy remains an active topic in current nanomedicine. Here, we designed a novel targeted theranostic nanoplatform for enhanced -weighted magnetic resonance (MR) imaging-guided chemotherapy by constructing layered double hydroxide (LDH)-stabilized ultrasmall iron oxide (FeO) nanoparticles with hyaluronic acid (HA) modified as targeting agents, and anticancer drug doxorubicin (DOX) loaded with a high loading efficiency. : The structure and release property of LDH-FeO-HA/DOX nanoplatforms were characterized systematically. B16 melanoma cells with CD44 receptors overexpressed were used as model cells to determine the biocompatibility, targeting capability, and therapeutic efficiency of nanoplatforms. For experiment, hyaluronidase (HAase) pretreatment was combined with nanoplatform administration to investigate the MR imaging and chemotherapeutic effect. : The LDH-FeO-HA nanohybrids possess good colloidal stability and cytocompatibility, display an relaxivity 10-fold higher than the pristine ultrasmall FeO (4.38 mM s 0.42 mM s), and could release drug in a pH-responsive manner. experiments demonstrate that LDH-FeO-HA/DOX nanohybrids are able to specifically target B16 cells overexpressing CD44 receptors and effectively release DOX to nucleus. results show that with the pretreatment of tumor tissue by HAase to degrade the overexpressed HA in extra-cellular matrix, the designed nanoplatforms have a better tumor penetration for significantly enhanced MR imaging of tumors and tumor chemotherapy with low side effects. : The designed LDH-FeO-HA/DOX nanohybrids may be developed as a novel targeted theranostic nanoplatform for enhanced -weighted MR imaging-guided chemotherapy of CD44 receptor-overexpressing tumors.
用于肿瘤成像和治疗的独特治疗性纳米平台的开发仍然是当前纳米医学中的一个活跃课题。在这里，我们设计了一种新型靶向治疗性纳米平台，通过构建具有透明质酸（HA）作为靶向剂的层状双氢氧化物（LDH）稳定的超小氧化铁（FeO）纳米粒子，并负载具有高载药效率的抗癌药物阿霉素（DOX），用于增强加权磁共振（MR）成像引导的化疗。系统地表征了 LDH-FeO-HA/DOX 纳米平台的结构和释放特性。使用过表达 CD44 受体的 B16 黑色素瘤细胞作为模型细胞，确定纳米平台的生物相容性、靶向能力和治疗效率。对于实验，结合透明质酸酶（HAase）预处理进行纳米平台给药，以研究 MR 成像和化疗效果。LDH-FeO-HA 纳米杂化物具有良好的胶体稳定性和细胞相容性，表现出比原始超小 FeO（4.38mM s 0.42mM s）高 10 倍的弛豫率，并且可以在 pH 响应方式下释放药物。实验表明，LDH-FeO-HA/DOX 纳米杂化物能够特异性靶向过表达 CD44 受体的 B16 细胞，并有效将 DOX 释放到细胞核。结果表明，通过 HAase 预处理肿瘤组织以降解细胞外基质中过表达的 HA，设计的纳米平台具有更好的肿瘤穿透性，可显著增强对肿瘤的 MR 成像和肿瘤化疗，并具有较低的副作用。设计的 LDH-FeO-HA/DOX 纳米杂化物可用作增强 CD44 受体过表达肿瘤的加权磁共振成像引导化疗的新型靶向治疗性纳米平台。
