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用于pH响应性和MRI引导化疗的聚多巴胺包覆的基于CPT@MIL-53(Fe)的诊疗纳米平台

PDA-coated CPT@MIL-53(Fe)-based theranostic nanoplatform for pH-responsive and MRI-guided chemotherapy.

作者信息

Zhou Chaohui, Yang Qingye, Zhou Xinyue, Jia Nengqin

机构信息

The Education Ministry Key Lab of Resource Chemistry, Joint International Research Laboratory of Resource Chemistry, Ministry of Education, Shanghai Frontiers Science Center of Biomimetic Catalysis, and Shanghai Key Laboratory of Rare Earth Functional Materials, College of Chemistry and Materials Science, Shanghai Normal University, Shanghai 200234, China.

出版信息

J Mater Chem B. 2022 Mar 16;10(11):1821-1832. doi: 10.1039/d1tb02339j.

Abstract

Theranostic nanoplatforms for multimodal diagnosis and treatment of tumors are a current research hotspot in the field of nanomedicine. MOF-based theranostic nanoplatforms integrating drug delivery with magnetic resonance imaging (MRI) have attracted broad attention in cancer diagnosis and therapy. However, due to the poor chemical and colloidal stability of MOFs, as well as their poor biocompatibility, MOF-based theranostic nanoplatforms still face critical challenges in cancer treatment applications. Here, we devised a theranostic nanoplatform based on a bioinspired polydopamine (PDA)-functionalized metal-organic framework MIL-53(Fe) loaded with camptothecin (CPT) for MRI-guided pH-sensitive chemotherapy. On the nanoplatform, MIL-53(Fe) with good biodegradability has large pore volume and showed a high loading content of antitumor drug CPT (43.07%). To overcome the disadvantages of poor aqueous solubility of MIL-53(Fe) and easy photodecomposition of CPT, the CPT-loaded MIL-53(Fe) was coated with a layer of PDA, resulting in theranostic nanoparticles (PDA@CPT@MIL-53(Fe)). The theranostic nanoparticles exhibited excellent stability and pH-sensitive drug release. toxicity studies showed that the nanoparticles could be efficiently taken up by breast cancer MCF-7 cells and exhibited high cytotoxicity. antitumor assay showed the great antitumor effect of the theranostic nanoparticles by using a zebrafish xenograft model. Furthermore, the incorporation of Fe affords the PDA@CPT@MIL-53(Fe) with potential MRI; MRI showed the nanoparticles exhibit an excellent MRI performance with an value up to 50 mM s. These results suggest that CPT-loaded MIL-53(Fe) coated with PDA is a promising theranostic platform for MRI imaging and cancer therapy.

摘要

用于肿瘤多模态诊断和治疗的诊疗纳米平台是纳米医学领域当前的研究热点。基于金属有机框架(MOF)的诊疗纳米平台将药物递送与磁共振成像(MRI)相结合,在癌症诊断和治疗中引起了广泛关注。然而,由于MOF的化学和胶体稳定性差,以及生物相容性不佳,基于MOF的诊疗纳米平台在癌症治疗应用中仍面临严峻挑战。在此,我们设计了一种基于生物启发的聚多巴胺(PDA)功能化金属有机框架MIL-53(Fe)的诊疗纳米平台,该平台负载喜树碱(CPT)用于MRI引导的pH敏感化疗。在该纳米平台上,具有良好生物降解性的MIL-53(Fe)具有大孔体积,并且显示出抗肿瘤药物CPT的高负载量(43.07%)。为了克服MIL-53(Fe)水溶性差和CPT易光分解的缺点,将负载CPT的MIL-53(Fe)用一层PDA包覆,得到诊疗纳米颗粒(PDA@CPT@MIL-53(Fe))。该诊疗纳米颗粒表现出优异的稳定性和pH敏感的药物释放。毒性研究表明,纳米颗粒能够被乳腺癌MCF-7细胞有效摄取并表现出高细胞毒性。抗肿瘤试验表明,通过斑马鱼异种移植模型,诊疗纳米颗粒具有显著的抗肿瘤效果。此外,铁的引入赋予PDA@CPT@MIL-53(Fe)潜在的MRI性能;MRI显示纳米颗粒具有优异的MRI性能,纵向弛豫率(r1)值高达50 mM-1 s-1。这些结果表明,用PDA包覆的负载CPT的MIL-53(Fe)是一种用于MRI成像和癌症治疗的有前景的诊疗平台。

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