Encapsidation of Different Plasmonic Gold Nanoparticles by the CCMV CP

Abstract

Different types of gold nanoparticles have been synthesized that show great potential in medical applications such as medical imaging, bio-analytical sensing and photothermal cancer therapy. However, their stability, polydispersity and biocompatibility are major issues of concern. For example, the synthesis of gold nanorods, obtained through the elongated micelle process, produce them with a high positive surface charge that is cytotoxic, while gold nanoshells are unstable and break down in a few weeks due to the Ostwald ripening process. In this work, we report the self-assembly of the capsid protein (CP) of cowpea chlorotic mottle virus (CCMV) around spherical gold nanoparticles, gold nanorods and gold nanoshells to form virus-like particles (VLPs). All gold nanoparticles were synthesized or treated to give them a negative surface charge, so they can interact with the positive N-terminus of the CP leading to the formation of the VLPs. To induce the protein self-assembly around the negative gold nanoparticles, we use different pH and ionic strength conditions determined from a CP phase diagram. The encapsidation with the viral CP will provide the nanoparticles better biocompatibility, stability, monodispersity and a new biological substrate on which can be introduced ligands toward specific cells, broadening the possibilities for medical applications.

Controlling the surface charge of simple viruses

“…The viruses can be self-assembled in vitro when the purified capsid protein (CP) and viral RNAs are mixed under appropriate buffer conditions [7]. Moreover, spontaneous assembly of VLPs can also take place around heterologous RNAs [8], anionic polymers [9], negatively charged nanoparticles [10], nanolipospheres [11], and even negatively charged nanoemulsion droplets [12], making VLPs potentially useful vehicles for gene and drug delivery.…”

The diversity of protein-protein interaction interfaces within T=3 icosahedral viral capsids

“…MS2 (Leviviridae) capsids have been used to design vessels for delivering therapeutic molecules (Wu et al, 1995;Brown et al, 2002;Wu et al, 2005;Galaway and Stockley, 2013;Yan et al, 2014;Pumpens et al, 2016) and for antigen presentation in vaccines (Mastico et al, 1993;Wu et al, 1995;Peabody, 1997;Tumban et al, 2015;Frietze et al, 2016;Pumpens et al, 2016). Similar studies have also been performed with T = 3 jelly-roll capsids (Ren et al, 2006;Barnhill et al, 2007;Lockney et al, 2011;Yildiz et al, 2012;Zeng et al, 2013;Sokullu et al, 2019;Durán-Meza et al, 2020). Understanding protein-protein interactions is an important step in improvising such systems, as was shown in a recent study on MS2 (Biela et al, 2022), where insertions were made to tweak the dimerization interface, allowing the formation of larger capsid structures.…”

“…In such assembly-disassembly processes, the balance of energetic interactions among CPs and between the CPs and the genome will determine the order of events in assembly. Capsids can also assemble around non-genome cargo ( Ren et al, 2006 ; Sokullu et al, 2019 ; Durán-Meza et al, 2020 ) indicating that CP-CP interactions can by themselves direct capsid assembly. In order to understand potential principles that govern such CP-CP interface energetics, we analyzed the strength and nature of all CP-CP interfaces ( Figures 1D–G ) in diverse T = 3 icosahedral viruses.…”

The Applications of Gold Nanoparticles in the Diagnosis and Treatment of Gastrointestinal Cancer

“…Many studies have recently focused on the combination of gold nanoparticles and biomolecules to treat or diagnose tumors ( 97 – 99 ), especially exosomes ( 100 , 101 ) ( Figure 5 ). Exosomes are vesicles secreted by cells that have a diameter of 30 - 100 nm and are formed in the endocrine pathway ( 102 , 103 ).…”