Controllable Synthesis of a Smart Multifunctional Nanoscale Metal–Organic Framework for Magnetic Resonance/Optical Imaging and Targeted Drug Delivery

Abstract

As a result of their extraordinarily large surfaces and well-defined pores, the design of a multifunctional metal-organic framework (MOF) is crucial for drug delivery but has rarely been reported. In this paper, a novel drug delivery system (DDS) based on nanoscale MOF was developed for use in cancer diagnosis and therapy. This MOF-based tumor targeting DDS was fabricated by a simple postsynthetic surface modification process. First, magnetic mesoporous nanomaterial Fe-MIL-53-NH was used for encapsulating the drug and served as a magnetic resonance contrast agent. Moreover, the Fe-MIL-53-NH nanomaterial exhibited a high loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, the fluorescence imaging agent 5-carboxyfluorescein (5-FAM) and the targeting reagent folic acid (FA) were conjugated to the 5-FU-loaded Fe-MIL-53-NH, resulting in the advanced DDS Fe-MIL-53-NH-FA-5-FAM/5-FU. Owing to the multifunctional surface modification, the obtained DDS Fe-MIL-53-NH-FA-5-FAM/5-FU shows good biocompatibility, tumor enhanced cellular uptake, strong cancer cell growth inhibitory effect, excellent fluorescence imaging, and outstanding magnetic resonance imaging capability. Taken together, this study integrates diagnostic and treatment aspects into a single platform by a simple and efficient strategy, aiming for facilitating new possibilities for MOF use for multifunctional drug delivery.

Folic Acid Functionalized Zirconium‐Based Metal–Organic Frameworks as Drug Carriers for Active Tumor‐Targeted Drug Delivery

“…In the synthesis of the NMOFs, different ratios of ligands and metal ions were used to obtain the optimal nanoscale products (see Table S1 and S2 in the Supporting Information). When the molar ratios of Zr 4+ and the ligand were 0.32:0.22 for MOF‐808 and 0.125:0.123 for NH 2 ‐UiO‐66, the particle sizes of the resulting products were both around 100 nm, as characterized by scanning electron microscopy (SEM; see Figures S1 and S2), which is superior to most of the reported MOF‐based targeting drug carriers reported in the literature . To prove the structures of the as‐synthesized NMOFs, FTIR spectroscopy and powder X‐ray diffraction (PXRD) analyses were carried out (see Figures S3–S6).…”

“…As for other types of drug carriers, attempts to introduce an active tumor targeting function have been successfully realized . In addition, attaching folic acid (FA) onto these drug carriers has proven to be effective for building an active targeting drug‐delivery system for tumors, due to the high concentration of folate receptor in tumor tissues …”

In Vivo Targeting and Positron Emission Tomography Imaging of Tumor with Intrinsically Radioactive Metal–Organic Frameworks Nanomaterials

“…On the other hand, although compelling evidence has been collected to prove that nMOFs can be readily used in multiple imaging techniques, such as computed tomography (CT), 17 magnetic resonance imaging (MRI), 18,19 or optical imaging, 20 very limited studies were carried out to date using nMOFs as in vivo tumor imaging agents. 21–23 …”

Nanoparticles of Metal‐Organic Frameworks: On the Road to In Vivo Efficacy in Biomedicine

“…Noteworthily, during the past 3–4 years, an increasing number of studies have highlighted the first in vivo benefits of nanoMOFs to treat different diseases in animal models. One can thus expect in the upcoming years exciting new developments concerning the preclinical in vivo evaluation of MOFs . A key condition of success will nevertheless require furthering strengthening the exchanges between chemists, pharmacists, and clinicians, for the creation of multidisciplinary projects dealing with the translation of nanoMOFs into more realistic biomedical solutions.…”