Hybrid organic-inorganic nanoparticles: controlled incorporation of gold nanoparticles into virus-like particles and application in surface-enhanced Raman spectroscopy

A capsid is the protein coat surrounding a virus' genome that ensures its protection and transport. The capsid of murine polyomavirus (muPy) consists of one major (VP1) and two minor (VP2/3) proteins, from which just VP1 is sufficient to form the capsid when expressed recombinantly (1). From a material engineering point of view, viral capsids are of interest because they present a paradigm for complex self-assembly on the nanometer scale. Understanding and controlling these assembly dynamics will allow the construction of nanoscale structures using a self-assembly process. The first step in this direction was the discovery that capsids of several viruses can be reversibly disassembled into their building blocks and reassembled using the same building blocks by simply changing the buffer conditions (2, 3). Such capsids already find applications as targeted in vivo delivery vectors for genes, proteins or small molecular drugs (4, 5), as optical probes for biomedical imaging and sensing purposes with unprecedented resolution and sensitivity and can potentially be used as templates for nanoelectronics (6, 7). Here we show the controlled incorporation of inorganic gold nanoparticles into the capsid shell of muPy. This incorporation is mediated by covalent sulfide bonds between the capsid proteins cysteine residues and the molecular gold. The number of incorporated gold particles can be controlled during the assembly process and the capsids retain their ability to transduce cells. These particles provide new tools for tracking of viral particles in cells, and simultaneously allow the delivery of genes packages in the hollow capsid.