Internalization of Metal–Organic Framework Nanoparticles in Human Vascular Cells: Implications for Cardiovascular Disease Therapy

Abstract

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Alteration of endothelial cells and the underlying vasculature plays a central role in the pathogenesis of various CVDs. The application of nanoscale materials such as nanoparticles in biomedicine has opened new horizons in the treatment of CVDs. We have previously shown that the iron metal–organic framework nanoparticle, Materials Institut Lavoisier-89 (nanoMIL-89) represents a viable vehicle for future drug delivery of pulmonary arterial hypertension. In this study, we have assessed the cellular uptake of nanoMIL-89 in pulmonary artery endothelial and smooth muscle cells using microscopy imaging techniques. We also tested the cellular responses to nanoMIL-89 using molecular and cellular assays. Microscopic images showed cellular internalization of nanoMIL-89, packaging into endocytic vesicles, and passing to daughter cells during mitosis. Moreover, nanoMIL-89 showed anti-inflammatory activity without any significant cytotoxicity. Our results indicate that nanoMIL-89 formulation may offer promising therapeutic opportunities and set forth a new prototype for drug delivery not only in CVDs, but also for other diseases yet incurable, such as diabetes and cancer.

Evaluation of Metal‐Organic Framework MIL-89 nanoparticles toxicity on embryonic zebrafish development

“…In this study, we used < 150 nm sized nanoMIL-89, which consists of an iron-based core-shell (iron (III) chloride hexahydrate) coordinated by organic linkers ( trans-trans muconic acid) [12] . NanoMIL-89 were prepared and characterized using powder X-ray diffraction (PXRD) and dynamic light scattering (DLS) as previously described by our group [12] , [27] . Briefly, iron (III) chloride hexahydrate (FeCl 3 .…”

“…Material Institute Lavoisier 89 nanoparticles (nanoMIL-89), a subclass of Metal-Organic Frameworks (MOFs), have been extensively studied for their preeminent porous crystalline structure, large surface area, and high conformational flexibility due to their metal (iron) oxide core and organic linkers [7] . These structural properties made nanoMIL-89 salient vehicle carriers for variant drugs, proteins, nucleic acids, and bioactive molecules [8] , [9] , [10] , [11] , [12] . However, despite the advantageous features of nanoMIL-89, they may represent a significant risk of toxicity, which could be attributed to leached iron metal ions leading to high stress in cells, tissue and organ damage, or developmental alterations that cannot be depicted from in vitro studies [13] , [14] .…”

“…We have previously synthesized and characterized a nano-formulation of MIL-89 and shown that at low concentrations (< 30 µg/mL) nanoMIL-89 has no harmful effects upon cellular internalization in a range of cell lines, including macrophages, epithelial, endothelial cells and smooth muscle cells [11] , [12] , [27] . However, the in vivo effects of nanoMIL-89 and their association with environmental health risks are unexplored [27] .…”

Metal-Organic Framework (MOF)-Based Biomaterials for Tissue Engineering and Regenerative Medicine

“…Evaluating non-copper based MOFs for cardiovascular implants, a MIL-101 (Fe) poly(ε−caprolactone) composite was investigated as material for metal free stents, using the MOF as mechanical re-enforcement, sustained drug release vehicle and Magnetic Resonance Imaging (MRI) contrast agent (Hamideh et al, 2020). Further, few studies exist that address the interaction of MOFs with cardiomyocytes (Al-Ansari et al, 2020). In vivo, Cu-BTC was shown effective as cardiovascular stent surface modification through coating together with polydopamine (Fan et al, 2019).…”

Metal–organic frameworks (MOFs) as host materials for the enhanced delivery of biomacromolecular therapeutics

“…(5) MOFs exhibit good biocompatibility and low cytotoxicity and can effectively penetrate the cell membrane of different types cells including liver cells, T cells, vascular cells, lung cells, germ cells, pancreatic cells, etc. [15][16][17][18][19][20][21] This is because MOFs exhibit high porosity and large specific surface area, which facilitates enhanced contact with the cell membranes, thereby increasing their uptake by cells. In addition, positively charged MOF materials can bind to cell membranes through electrostatic interactions and thus can enter cells by endocytosis.…”