Site-Selective Nucleation and Size Control of Gold Nanoparticle Photothermal Antennae on the Pore Structures of a Virus

J Am Chem Soc. 2018 Dec 12;140(49):17226-17233. doi: 10.1021/jacs.8b10446. Epub 2018 Nov 29.

Abstract

In this Article, we show that the surface of the bacteriophage Qβ is equipped with natural ligands for the synthesis of small gold nanoparticles (AuNPs). By exploiting disulfides in the protein secondary structure and the geometry formed from the capsid quaternary structure, we find that we can produce regularly arrayed patterns of ∼6 nm AuNPs across the surface of the virus-like particle. Experimental and computational analyses provide insight into the formation and stability of this composite. We further show that the entrapped genetic material can hold upward of 500 molecules of the anticancer drug Doxorubicin without leaking and without interfering with the synthesis of the AuNPs. This direct nucleation of nanoparticles on the capsid allows for exceptional conduction of photothermal energy upon nanosecond laser irradiation. As a proof of principle, we demonstrate that this energy is capable of rapidly releasing the drug from the capsid without heating the bulk solution, allowing for highly targeted cell killing in vitro.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • A549 Cells
  • Allolevivirus / chemistry*
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Capsid / chemistry
  • Capsid Proteins / chemistry
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Carriers / chemistry*
  • Drug Carriers / radiation effects
  • Drug Carriers / toxicity
  • Drug Liberation
  • Gold / chemistry*
  • Gold / radiation effects
  • Gold / toxicity
  • Humans
  • Hyperthermia, Induced / methods
  • Light
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / radiation effects
  • Metal Nanoparticles / toxicity
  • Mice
  • Particle Size
  • Phototherapy / methods
  • Porosity
  • Proof of Concept Study
  • RAW 264.7 Cells
  • RNA / chemistry
  • RNA / toxicity

Substances

  • Antineoplastic Agents
  • Capsid Proteins
  • Drug Carriers
  • RNA
  • Gold
  • Doxorubicin