Biomimetic Nucleation of Metal–Organic Frameworks on Silk Fibroin Nanoparticles for Designing Core–Shell-Structured pH-Responsive Anticancer Drug Carriers
Yuping Chen, Hesong Wu, Tao Yang, Guanshan Zhou, Yuyin Chen, Jie Wang, Chuanbin Mao, Mingying Yang
Abstract
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.