Nanoscale Zr‐Based MOFs with Tailorable Size and Introduced Mesopore for Protein Delivery

Abstract

Introduction of large pore in the primitive microporous metal–organic frameworks (MOFs) with tailorable particle size can endow them with desired properties for potential applications in the intracellular delivery of membrane‐impermeable proteins. However, no research is found to focus on this topic until now. Herein, a monocarboxylic acid (MA) and organic base comodulation strategy is developed to synthesize the hierarchically porous UiO‐66 nanoparticles. MA of dodecanoic acid is utilized to control the pore size while trimethylamine (TEA) plays a key role in modulating the nucleation of crystallization to regulate the particle size. In comparison with microporous UiO‐66, a model protein of cytochrome c (Cyt c) could be efficiently loaded into the mesoporous MOFs (mesoMOFs). The size‐dependent cellular uptake is also evaluated, and it is verified that mesoMOFs with particle size of 90 nm could be endocytosed into living cells with highest efficiency. These outstanding merits enable the current mesoMOFs not only to exhibit efficient encapsulation of Cyt c but also facilitate the protein delivery into the cytosol and subsequent endosomal escape. Given the exceptional chemical stability, hierarchically porous structure as well as tunable particle size, the elaborated mesoUiO‐66 nanoparticles might offer a promising platform for a variety of biomedical applications.

Templated fabrication of hierarchically porous metal–organic frameworks and simulation of crystal growth

“…15,16 However, the pores of most available MOFs to date have belonged to a pure microporous regime (pore size < 2 nm), 17 which would impede the diffusion rate and restrict the accessibility of guest molecules toward the active sites within the internal space of MOFs, especially for biomacromolecules. 18 Therefore, it is of great importance to develop an effective and reliable strategy to transform microporous MOFs into their hierarchical porous counterparts with micropores and mesopores.…”

Mitochondria‐Targeted Nanoscale MOFs for Improved Photodynamic Therapy

“…To ensure that the optical properties of TCPP as PS molecules are maintained, UV‐vis and fluorescent spectra were recorded on UiO‐66‐TCPP nanoparticles. As shown in Figure S5, five characteristic UV‐vis absorption peaks are observed at 419 nm (strong peak), 521 nm, 560 nm, 588 nm and 648 nm (weak peaks), which are corresponding to one Soret band and four Q bands of TCPP, respectively . Additionally, upon the excitation at 520 nm, an intense red emission could be observed for UiO‐66‐TCPP as shown in Figure S6, which could be attributed to the diminished aggregation‐induced quenching effect caused by the dispersive distribution of TCPP molecules isolated by Zr−O clusters .…”

Water-based routes for synthesis of metal-organic frameworks: A review

“…There has been a substantial increase in interest of MOFs owing to their attractive physicochemical characteristics such as high surface area, permanent porosity, abundant active sites, and flexible chemical structure [4][5][6][7][8][9]. To date, the main focus of MOF investigations is the optimization of their structures or properties, such as increasing the crystallinity and pore size, to develop their potential applications in gas storage [10][11][12][13], adsorption and separation [14][15][16][17], large molecule encapsulation [18][19][20], supercapacitors [21][22][23], energy conversion [24,25], chemical sensors [26][27][28], biomedicine [29,30], and catalysis [31][32][33]. However, the synthesis conditions of MOFs for eco-friendly and industrial scale-up were only sparsely investigated in both research and industrial laboratories [34,35].…”