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.

MIPs for commercial application in low-cost sensors and assays – An overview of the current status quo

“…The dose-response curve for this system displayed a wide linear range (0–1.2 × 10 −6 M) even in the presence of common ionic and molecular interfaces that can be found in biofluids, yielding an LoD of 100−150 × 10 -9 M. All results were validated with HPLC, which emphasizes that the assay is not only interesting because it is handheld and requires little instrumentation but also has enough diagnostic relevance. Over the past two years alone, many similar QD-based MIP assays have been developed for various purposes including medical diagnostics [ [216] , [217] , [218] ], food safety [ 219 , 220 ] and environmental screening [ 221 , 222 ].

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Metal‐Organic Frameworks‐Based Fluorescent Nanocomposites for Bioimaging in Living Cells and in vivo†

“…Li and co‐workers have constructed a biodegradable nanoplatform of MIP‐stabilized fluorescent ZIF‐8 (FZIF‐8/ DOX‐MIPs) for targeted imaging and GSH/pH dual stimulation drug release. [ 100 ] It is worth noting that carbon dots emitted strong red fluorescence which promotd targeted imaging of tumor cells (Figure 6). The fluorescent signal of FZIF‐8/DOX‐MIPs gradually increased in the tumor site of mice with time.…”

“…(D) Fluorescence images of mice with MCF‐7 tumors at different times after intraperitoneal injection of two different nanoparticles. Reprinted with permission, [ 100 ] Copyright 2020, American Chemical Society.…”

Molecularly imprinted materials for biomedical sensing

“…In this scenario, the devel- Tumour imaging and treatment. Qin et al (2020) sensitivity of fluorescence measurements with the high selectivity provided by MIPs. Useful applications of MIPs as artificial receptors facilitating imaging were recently reviewed (Vaneckova et al, 2020).…”