Tumor-Sensitive Biodegradable Nanoparticles of Molecularly Imprinted Polymer-Stabilized Fluorescent Zeolitic Imidazolate Framework-8 for Targeted Imaging and Drug Delivery.

Abstract

Targeting enrichment of nanocarriers at tumor sites and effective drug release are critical in cancer treatment. Accordingly, we used fluorescent zeolitic imidazolate framework-8 nanoparticles loaded with doxorubicin (FZIF-8/DOX) as the core and a molecularly imprinted polymer (MIP) as the shell to synthesize tumor-sensitive biodegradable FZIF-8/DOX-MIP nanoparticles (FZIF-8/DOX-MIPs). The MIP prepared with the epitope of CD59 cell membrane glycoprotein as the template allowed FZIF-8/DOX-MIPs to be enriched to tumor sites by actively targeting recognition of MCF-7 cancer cells (CD59-positive). Moreover, using N,N'-diacrylylcystamine as the cross-linker and dimethylaminoethyl methacrylate as the main monomer, the MIP's framework will be broken under the stimulation of a tumor microenvironment (high-concentration glutathione and weakly acidic), so that the internal FZIF-8/DOX is exposed to a microacidic environment to release DOX through further degradation. More importantly, the ability of FZIF-8/DOX-MIPs in targeted fluorescence imaging and effective drug release has been validated both in vitro and in vivo. Compared to other cells and nanoparticles, FZIF-8/DOX-MIPs were more capable of being phagocytosed by MCF-7 cells and were more lethal to MCF-7 cells. In the comparative experiments carried out on tumor-bearing mice, FZIF-8/DOX-MIPs had the best inhibitory effect on the growth of MCF-7 tumors. Furthermore, the FZIF-8/DOX-MIPs can serve as a diagnostic agent because of the active targeting of MCF-7 cells and the stronger red fluorescence of the embedded carbon quantum dots. Because of the active targeting ability, good biocompatibility, tumor-sensitive biodegradability, and effective drug release performance, FZIF-8/DOX-MIPs can be widely used in tumor imaging and treatment.