Comb-like dextran copolymers: A versatile strategy to coat highly porous MOF nanoparticles with a PEG shell

Abstract

Nanoparticles made of metal-organic frameworks (nanoMOFs) are becoming of increasing interest as drug carriers. However, preventing nanoMOFs recognition and clearance by the innate immune system, a prerequisite for biomedical applications, presents an important challenge. In this study we provide a proof of concept that the outer surface of biocompatible iron-based nanoMOFs can be functionalized in a rapid, organic solvent-free and non-covalent manner using a novel family of comb-like copolymers made of dextran (DEX) grafted with both poly(ethylene glycol) (PEG) and alendronate (ALN) moieties. We describe the synthesis and full characterization of DEX-PEG-ALN copolymers by click chemistry, with control of both the amount of grafted PEG and ALN moieties. The copolymers, freely soluble in aqueous media, were used to directly coat the nanoMOFs in water by simple incubation at room temperature. The coating procedure did not affect the nanoMOFs' morphology nor their crystalline structure. As strong iron complexing groups, the ALN moieties ensured multiple cooperative anchoring of the copolymers to the nanoMOFs surface, resulting in stable coatings that substantially decreased their internalization by macrophages in vitro, providing new perspectives for biomedical applications.

Drug-Loaded Lipid-Coated Hybrid Organic-Inorganic “Stealth” Nanoparticles for Cancer Therapy

“…Interestingly, lipid coating dramatically reduced HSA adsorption, to only ∼5 µg HSA/mg nanoMOFs ( Figure 8A, green curve), regardless of the addition of DSPE-PEG 2000 ( Figure 8A, red curve). To the best of our knowledge, these adsorbed HSA amounts are among the lowest reported with MIL-100 (Fe) nanoMOFs (Gref et al, 2000;Cutrone et al, 2019b), suggesting that lipid-based coating on nanoMOFs is efficient to avoid albumin adsorption.…”

“…Indeed, the ZP of the uncoated nanoMOFs was strongly dependent upon the pH of the suspension medium, shifting from positive values (+ 23 ± 3 mV) at pH lower than 5 to negative values (−15 ± 3 mV) at basic pH. This could be probably due to the presence of both uncoordinated iron sites and terminal carboxyl groups of the trimesate ligands at the external nanoMOFs surface (Cutrone et al, 2019b). The ZP values were dramatically altered after surface modification ( Figure 3C).…”

“…Quantitative data on the amounts of nanoMOFs internalized by cells were obtained by ICP-MS, after extensive washing to remove the non-associated particles. An incubation time of 4 h was chosen as it corresponds to the typical blood circulation time of PEG-coated NPs (Cutrone et al, 2019b). Interestingly, the DOPC coating of nanoMOFs reduced their macrophage uptake by a factor of 2.4, from 75 ± 6% to 31 ± 3% ( Figure 8B).…”

“…Alternatively, nanoMOFs were coated with inclusion complexes consisting of functionalized cyclodextrins (CDs) and PEG chains coupled to adamantine ( Agostoni et al, 2015 ; Aykac et al, 2017 ; Cutrone et al, 2019a ). Finally, comb-like copolymers consisting of polysaccharides grafted with moieties able to coordinate to the nanoMOFs and PEG chains were synthesized and anchored onto the nanoMOFs ( Cutrone et al, 2019b ). However, all these coatings imply sophisticated chemistry strategies and/or several preparation steps, which might restrict their further applications.…”

Designing Magnetic NanoMOFs for Biomedicine: Current Trends and Applications

“…Interestingly, a targeting strategy based on the pH-induced aggregation of the MIL-100(Fe) nanoMOF was proposed by Simon-Yarza et al for lung tissues [62], which demonstrates the key role of aggregation/agglomeration phenomena in biomedical applications also for magnetic nanoMOFs as for magnetic nanoparticles. Besides size-related research, studies on nanoMOF morphology and surface functionalization [63][64][65][66][67][68] are also reported in the literature. Figure 3 summarizes the specific theranostic abilities, i.e., multimodal imaging capability and combined chemo-photothermal therapy, required to develop a promising next-generation class of theranostic nanoagents for FOI (Fluorescence Optical Imaging) and MRI along with synchronous, efficient and safe (low-toxicity) cancer therapy.…”