Biomimetic Nucleation of Metal–Organic Frameworks on Silk Fibroin Nanoparticles for Designing Core–Shell-Structured pH-Responsive Anticancer Drug Carriers,ACS Applied Materials & Interfaces

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Biomimetic Nucleation of Metal–Organic Frameworks on Silk Fibroin Nanoparticles for Designing Core–Shell-Structured pH-Responsive Anticancer Drug Carriers
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-09-28 , DOI: 10.1021/acsami.1c13405
Yuping Chen ₁ , Hesong Wu ₁ , Tao Yang ₂ , Guanshan Zhou ₁ , Yuyin Chen ₁ , Jie Wang ₁ , Chuanbin Mao _{2,

3} , Mingying Yang ₁

Affiliation

Silk fibroin (SF) is a biomacromolecule that can be assembled into nanostructures and induce biomimetic nucleation of inorganic materials. Zeolitic imidazolate framework-8 (ZIF-8), a metal–organic framework (MOF), can be dissolved selectively under acidic pH. Here, we integrated SF and ZIF-8 to develop novel drug carriers that selectively release drug in the acidic intracellular environment of cancer cells. Specifically, SF was assembled into nanoparticles (SF-NPs), which were then loaded with an antitumor drug, doxorubicin (DOX), to form DSF-NPs. Due to the SF-mediated organization of ZIF-8 precursors such as zinc ions, the DSF-NPs further templated the nucleation of ZIF-8 onto their surface to generate core–shell-structured NPs (termed DSF@Z-NPs) with ZIF-8 as a shell and DSF-NP as a core. We found that the DSF@Z-NPs, highly stable under neutral conditions, could be uptaken by breast cancer cells, release DOX selectively owing to dissolution of ZIF-8 shells in the acidic intracellular environment in a controlled manner, and induce cell apoptosis. We also confirmed that the DSF@Z-NPs could inhibit tumor growth more efficiently to reach a higher survival rate than their controls by inducing cell apoptosis in vivo. Our study suggests that SF and MOF could be combined to design a new type of cancer therapeutics.

中文翻译：

丝素蛋白纳米粒子上金属有机框架的仿生成核用于设计核壳结构 pH 响应性抗癌药物载体

丝素蛋白（SF）是一种生物大分子，可以组装成纳米结构并诱导无机材料仿生成核。沸石咪唑酯骨架-8 (ZIF-8) 是一种金属有机骨架 (MOF)，可以在酸性 pH 下选择性溶解。在这里，我们整合SF和ZIF-8来开发新型药物载体，在癌细胞的酸性细胞内环境中选择性释放药物。具体来说，SF被组装成纳米颗粒（SF-NPs），然后负载抗肿瘤药物阿霉素（DOX），形成DSF-NPs。由于锌离子等 ZIF-8 前体的 SF 介导组织，DSF-NP 进一步将 ZIF-8 成核模板化到其表面，以 ZIF 生成核壳结构的 NP（称为 DSF@Z-NP） -8为壳，DSF-NP为核。我们发现DSF@Z-NPs在中性条件下高度稳定，可以被乳腺癌细胞摄取，由于ZIF-8壳在细胞内酸性环境中以受控方式溶解而选择性释放DOX，并诱导细胞凋亡。我们还证实，DSF@Z-NPs 可以通过诱导体内细胞凋亡，更有效地抑制肿瘤生长，从而比对照获得更高的存活率。我们的研究表明，SF 和 MOF 可以结合起来设计一种新型的癌症疗法。

更新日期：2021-10-13

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