Self‐Assembly of Proteinaceous Shells around Positively Charged Gold Nanomaterials Enhances Colloidal Stability in High‐Ionic‐Strength Buffers

Abstract

The enzyme lumazine synthase (LS) has been engineered to self‐assemble into hollow‐shell structures that encapsulate unnatural cargo proteins through complementary electrostatic interactions. Herein, we show that a negatively supercharged LS variant can also form organic–inorganic hybrids with gold nanomaterials. Simple mixing of LS pentamers with positively charged gold nanocrystals in aqueous buffer spontaneously affords protein‐shelled gold cores. The procedure works well with differently sized and shaped gold nanocrystals, and the resulting shelled complexes exhibit dramatically enhanced colloidal stability over a wide range of pH (4.0–10.0) and at high ionic strength (up to 1 m NaCl). They are even stable over days upon dilution in buffer. Self‐assembly of engineered LS shells in this way offers an easy and attractive alternative to commonly used ligand‐exchange methods for stabilizing inorganic nanomaterials.

State of the Art and Prospects for Halide Perovskite Nanocrystals

“…Perovskite materials can be driven to self-assembly into 1D, 2D or 3D superlattices which has given rise to focused research on targeted functionalization of low dimensional perovskites and perovskite NC superlattice structures. ,,,,,− Improved strategies to control shape and size have been found in recent years and targeted tuning is within reach. , As more methods for self-assembly and directed superlattice growth of NCs become available also the need for more detailed structural, superstructural and morphological characterization techniques arises. Long-range ordering of the NCs leads to a scattering signal.…”

Polyelectrolyte Encapsulation and Confinement within Protein Cage-Inspired Nanocompartments

“…The same cage also successfully encapsulated engineered ferritin cages that possessed a positively charged surface, forming a Matryoshka-type complex [81]. Aside from the intact cage, AaLS-13 pentamers were found to effectively bind positively charged AuNPs through electrostatic interactions, producing a core-shell structure with enhanced colloidal stability over a wide range of pH and ionic strength [82].…”

“…Pharmaceutics 2021, 13, x FOR PEER REVIEW 13 of 23 core-shell structure with enhanced colloidal stability over a wide range of pH and ionic strength [82]. The AaLS-based charge complementary system can be reversed through the introduction of positively charged mutations or arginine-rich motifs in the lumen.…”

Protein Cages: From Fundamentals to Advanced Applications

“…391 Although inorganic nanoparticles possess promising properties for imaging and therapy, they are often unstable in biological sera and buffers of even moderate ionic strength. Coating these nanoparticles with a protein shell provides a means to both stabilize the nanoparticles 392,393 and in some cases impart the cellular uptake properties of the parent virus. 394 While the positively charged lumen of viral capsids naturally allows nonspecific electrostatically driven self-assembly, 33,34,388,392,395 other more nuanced strategies can be used to drive nanoparticle encapsulation.…”

“…907 Encapsulation of small-molecule cargo can be achieved by either covalent or non-covalent methods, which are generally carried out in vitro as for other synthetic cargo, such as nanoparticles. 33,34,393,397 Chemical conjugation is an effective way to load protein cages with small molecules. An important criterion for internal conjugation is that the capsid has some degree of porosity, allowing the reactive molecules into the interior where they can form covalent bonds with target residues (Figure 25a).…”