Metal–Phenolic Coatings as a Platform to Trigger Endosomal Escape of Nanoparticles

Abstract

The intracellular delivery of functional nanoparticles (NPs) and the release of therapeutic payloads at a target site are central issues for biomedical applications. However, the endosomal entrapment of NPs typically results in the degradation of active cargo, leading to poor therapeutic outcomes. Current advances to promote the endosomal escape of NPs largely involve the use of polycationic polymers and cell-penetrating peptides (CPPs), which both often suffer from potential toxicity and convoluted synthesis/conjugation processes. Herein, we report the use of metal-phenolic networks (MPNs) as versatile and nontoxic coatings to facilitate the escape of NPs from endo/lysosomal compartments. The MPNs, which were engineered from the polyphenol tannic acid and Fe III or Al III , enabled the endosomal escape of both inorganic (mesoporous silica) and organic (polystyrene and melamine resin) NPs owing to the "proton-sponge effect" arising from the buffering capacity of MPNs. Postfunctionalization of the MPN-coated NPs with low-fouling polymers did not impair the endosomal escape, indicating the modular and generalizable nature of this approach. We envisage that the ease of fabrication, versatility, low cytotoxicity, and promising endosomal escape performance displayed by the MPN coatings offer opportunities for such coatings to be used for the efficient delivery of cytoplasm-targeted therapeutics using NPs.

Particle engineering enabled by polyphenol-mediated supramolecular networks

“…Compared to other polyphenol-based supramolecular systems, such as chelation-based nanoparticles (NPs) 24 , the pBDT-TA supramolecular networks allow tailoring of particle size, and they are stable in harsh aqueous environments (chelation-based materials typically disassemble in acid conditions 25 ). Thus, the pBDT-TA particles are envisioned to provide additional versatility and functionality for engineering NPs, while also affording a number of opportunities for subsequent modification.…”

Polyphenol‐Containing Nanoparticles: Synthesis, Properties, and Therapeutic Delivery

“…Apart from the above biomedical applications, the polyphenolcontaining materials were also applied for treating peripheral artery disease, [232] facilitating the endosomal escape and the controlled pulmonary deposition of NPs, [233,234] controlling hemostasis, [235] etc. The recent years have witnessed a surge in the number of polyphenol-containing nanomaterials for a very broad range of biomedical applications, and it is believed that more interesting and important applications are emerging now and will emerge in the near future in the related field.…”

Polyphenol-Mediated Assembly for Particle Engineering

“…5,6 In the last decade, our group has explored a variety of polyphenol-mediated assemblies for materials engineering (Figure 1). [7][8][9][10][11][12][13][14][15][16][17][18][19] In the present Account, the term "polyphenol" is used to refer to catechol-and gallol-containing aromatic building blocks with functionality common to polyphenols, without distinction between natural polyphenols and their synthetic derivatives.…”