Manganese-Zeolitic Imidazolate Frameworks-90 with High Blood Circulation Stability for MRI-Guided Tumor Therapy
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ARTICLE
Cite as Nano-Micro Lett. (2019) 11:61 Received: 19 May 2019 Accepted: 29 June 2019 © The Author(s) 2019
https://doi.org/10.1007/s40820-019-0292-y
Manganese‑Zeolitic Imidazolate Frameworks‑90 with High Blood Circulation Stability for MRI‑Guided Tumor Therapy Zhenqi Jiang1,3, Bo Yuan1, Nianxiang Qiu1, Yinjie Wang1,3, Li Sun1,3, Zhenni Wei1, Yanyin Li1,3, Jianjun Zheng2, Yinhua Jin2, Yong Li1, Shiyu Du1, Juan Li1 *, Aiguo Wu1 * Zhenqi Jiang and Bo Yuan contributed equally to this work. * Juan Li, [email protected]; Aiguo Wu, [email protected] Cixi Institute of Biomedical Engineering, CAS Key Laboratory of Magnetic Materials and Devices & Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, People’s Republic of China
1
2
3
Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, People’s Republic of China University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China
HIGHLIGHTS • Manganese-zeolitic imidazolate frameworks (Mn-ZIF-90) with both high drug loading and magnetic resonance imaging (MRI) in vitro and in vivo were prepared. • The modification of a newly designed pH-protective and active-targeting Y1 receptor ligand reduces the drug release during blood circulation and specifically targets the tumor sites, improving therapeutic efficacy in vivo. • The combination of nano-size Mn-ZIF-90 and the highly specific Y1 receptor ligand promotes the specific drug accumulation in tumor sites.
ABSTRACT Zeolitic imidazolate frameworks (ZIFs) as smart drug delivery systems with
Less drug release during blood circulation
microenvironment-triggered release have attracted much attention for tumor therapy. However,
the exploration of ZIFs in biomedicine still encounters many issues, such as inconvenient surface modification, fast drug release during blood circulation, undesired damage to major organs, and
Tumor
severe in vivo toxicity. To address the above issues, we developed an Mn-ZIF-90 nanosystem functionalized with an originally designed active-targeting and pH-responsive magnetic resonance imaging (MRI) Y1 receptor ligand [Asn28, Pro30, Trp32]-NPY (25–36) for imaging-guided
tumor therapy. After Y1 receptor ligand modification, the Mn-ZIF-90 nanosystem exhibited
Cell membrane & mitochondria dual targeting
MR imaging guided tumor therapy
high drug loading, better blood circulation stability, and dual breast cancer cell membrane and mitochondria targetability, further favoring specific microenvironment-triggered tumor therapy. Meanwhile, this nanosystem showed promising T 1-weighted magnetic resonance imaging con-
trast in vivo in the tumor sites. Especially, this nanosystem with fast clean-up had almost no obvious toxicity and no damage occurred to the major organs in mice. Therefore, this nanosystem shows potential for use in imaging-guided tumor therapy. KEYWORDS Zeolitic imidazolate frameworks-90; Drug delivery; Magnetic r
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