Drug-Loaded Lipid-Coated Hybrid Organic-Inorganic "Stealth" Nanoparticles for Cancer Therapy.

Xue Li,Mathilde Menard,Ruxandra Gref,Theodossis Theodossiou,Kristian Berg,Jingwen Qiu,Giuseppina Salzano,Catherine Ladavière

doi:10.3389/fbioe.2020.01027

Abstract

Hybrid porous nanoscale metal organic frameworks (nanoMOFs) made of iron trimesate are attracting increasing interest as drug carriers, due to their high drug loading capacity, biodegradability, and biocompatibility. NanoMOF surface modification to prevent clearance by the innate immune system remains still challenging in reason of their high porosity and biodegradable character. Herein, FDA-approved lipids and poly(ethylene glycol) (PEG)-lipid conjugates were used to engineer the surface of nanoMOFs by a rapid and convenient solvent-exchange deposition method. The resulting lipid-coated nanoMOFs were extensively characterized. For the first time, we show that nanoMOF surface modification with lipids affords a better control over drug release and their degradation in biological media. Moreover, when loaded with the anticancer drug Gem-MP (Gemcitabine-monophosphate), iron trimesate nanoMOFs acted as “Trojan horses” carrying the drug inside cancer cells to eradicate them. Most interestingly, the PEG-coated nanoMOFs escaped the capture by macrophages. In a nutshell, versatile PEG-based lipid shells control cell interactions and open perspectives for drug targeting.

Highlights

Despite progresses in drug development and cancer biology, cancer mortality rate remains over 30%, and the morbidity much higher
Iron trimesate nanoMOFs with mean diameters of 232 ± 14 nm and Brunauer–Emmett–Teller (BET) surface areas of 1519 ± 50 m2.g−1 were successfully synthesized by a “green” organic solvent-free hydrothermal method exempt of toxic additives such as hydrofluoric acid (Agostoni et al, 2013)
In an attempt to achieve “stealth” NPs, the as-synthesized nanoMOF were surface functionalized with poly(ethylene glycol) (PEG)-lipid conjugates in a one-step procedure using a mixture of DSPE-PEG 2000 and DOPC

Summary

Introduction

Despite progresses in drug development and cancer biology, cancer mortality rate remains over 30%, and the morbidity much higher. Iron (III) trimesate nanoMOFs (Figure 1 upper panel) are among the most widely studied MOFs for drug delivery (Horcajada et al, 2010; Agostoni et al, 2013; Baati et al, 2013; SimonYarza et al, 2016; Li et al, 2019a) They were shown to display several intrinsic properties of main interest in the nanomedicine field: radio-enhancement properties when submitted to γ-irradiation (Li et al, 2019a); they behaved as T2weighted MRI imaging contrast agents (Horcajada et al, 2010) and they had intrinsic antibacterial effects killing intracellular bacteria (Li et al, 2019b)

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Results

Conclusion