Acta Biomaterialia ( IF 9.4 ) Pub Date : 2021-10-10 , DOI: 10.1016/j.actbio.2021.10.006 Heze Guo 1 , Lingshan Liu 1 , Qiangqiang Hu 1 , Hongjing Dou 1
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Impressive developments have been achieved with the use of zeolitic imidazolate framework-8 (ZIF-8) as nanocarriers for tumor theranostics in recent decades by incorporating imaging agents and therapeutic drugs within ZIF-8. However, the simultaneous immobilization of hydrophilic and hydrophobic functional molecules into ZIF-8 nanoparticles in water or organic solvents still presents a daunting challenge. Herein, we developed a new synthesis/encapsulation two-in-one (denoted as one-pot) approach to synthesize uniform dextran-modified Cy5.5&ICG@ZIF-8-Dex nanoparticles in DMSO/H2O solvent mixtures, which enabled the simultaneous encapsulation of hydrophilic indocyanine green (ICG) and hydrophobic cyanine-5.5 (Cy5.5) during the same step. It was confirmed that the one-pot approach in this mixed solvents facilitated the loading of ICG and Cy5.5 molecules. Moreover, the encapsulation of Cy5.5 and ICG within ZIF-8 nanoparticles endowed them with fluorescence imaging capability and photothermal conversion capacity, respectively. The in vivo near-infrared (NIR) fluorescent images of A549-bearing mice injected with Cy5.5&ICG@ZIF-8-Dex demonstrated sufficient accumulations of Cy5.5 at tumor sites due to the enhanced permeability and retention effect. Most impressively, the fluorescent intensity of Cy5.5&ICG@ZIF-8-Dex at tumor site was approximately 40-fold higher than that of free Cy5.5. Additionally, the results of in vivo infrared imaging and photothermal therapy of Cy5.5&ICG@ZIF-8-Dex showed enhanced therapeutic efficiency in comparison with free ICG, further confirming its tumor-targeting capability and photothermal capacity. Therefore, this multifunctional system based on ZIF-8 nanocarriers offered a potential nanoplatform for tumor-targeting theranostics, thus broadening the synthesis and applications of ZIF-8 composite nanoparticles for NIR fluorescence imaging and photothermal therapy in the biomedical field.
Statement of significance
Simultaneous immobilization of hydrophilic and hydrophobic molecules into ZIF-8 nanoparticles still remains a daunting challenge. Therefore, we have developed a new synthesis/encapsulation two-in-one approach to synthesize uniform Cy5.5&ICG@ZIF-8-Dex composite nanoparticles in DMSO/H2O solvent mixtures, which enabled the simultaneous encapsulation of hydrophilic indocyanine green (ICG) and hydrophobic cyanine-5.5 (Cy5.5) functional molecules during a single step. The results showed that the co-loading of Cy5.5 and ICG within the ZIF-8 nanoparticles endowed them with a remarkable fluorescence imaging capability and photothermal conversion capacity. Based on their enhanced convenience and efficacy to simultaneously encapsulate hydrophilic and hydrophobic molecules, the multifunctional nanocarriers that were prepared in the DMSO/H2O mixed solvents provide a potential nanoplatform toward fluorescence imaging and photothermal therapy for tumor theranostics.
中文翻译：
单分散 ZIF-8@dextran 纳米颗粒共负载亲水和疏水功能货物，用于组合近红外荧光成像和光热治疗
近几十年来，通过在 ZIF-8 中加入显像剂和治疗药物，使用沸石咪唑酯框架 8 (ZIF-8) 作为肿瘤治疗学的纳米载体，取得了令人瞩目的发展。然而，在水或有机溶剂中同时将亲水和疏水功能分子固定到 ZIF-8 纳米颗粒中仍然是一项艰巨的挑战。在此，我们开发了一种新的合成/封装二合一（表示为一锅法）方法，用于在 DMSO/H 2中合成均匀的葡聚糖修饰的 Cy5.5&ICG@ZIF-8-Dex 纳米粒子O 溶剂混合物，这使得在同一步骤中能够同时封装亲水性吲哚菁绿 (ICG) 和疏水性 cyanine-5.5 (Cy5.5)。已经证实，在这种混合溶剂中的一锅法促进了 ICG 和 Cy5.5 分子的加载。此外，Cy5.5 和 ICG 在 ZIF-8 纳米颗粒中的封装分别赋予了它们荧光成像能力和光热转换能力。体内_注射 Cy5.5&ICG@ZIF-8-Dex 的 A549 小鼠的近红外 (NIR) 荧光图像显示，由于增强的渗透性和滞留效应，Cy5.5 在肿瘤部位有足够的积累。最令人印象深刻的是，Cy5.5&ICG@ZIF-8-Dex 在肿瘤部位的荧光强度比游离 Cy5.5 高约 40 倍。此外，体内结果与游离 ICG 相比，Cy5.5&ICG@ZIF-8-Dex 的红外成像和光热治疗显示出更高的治疗效率，进一步证实了其肿瘤靶向能力和光热能力。因此，这种基于 ZIF-8 纳米载体的多功能系统为肿瘤靶向治疗提供了潜在的纳米平台，从而拓宽了 ZIF-8 复合纳米粒子在生物医学领域用于近红外荧光成像和光热治疗的合成和应用。
重要性声明
将亲水和疏水分子同时固定到 ZIF-8 纳米颗粒中仍然是一项艰巨的挑战。因此，我们开发了一种新的合成/封装二合一方法，在 DMSO/H 2中合成均匀的 Cy5.5&ICG@ZIF-8-Dex 复合纳米粒子O 溶剂混合物，可在一个步骤中同时封装亲水性吲哚菁绿 (ICG) 和疏水性 cyanine-5.5 (Cy5.5) 功能分子。结果表明，Cy5.5 和 ICG 在 ZIF-8 纳米颗粒中的共同负载赋予它们显着的荧光成像能力和光热转换能力。基于其增强的同时封装亲水和疏水分子的便利性和有效性，在 DMSO/H 2 O 混合溶剂中制备的多功能纳米载体为肿瘤治疗学的荧光成像和光热治疗提供了潜在的纳米平台。
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