Chimeric virus-like particles made using GAG and M1 capsid proteins providing dual drug delivery and vaccination platform

Mol Pharm. 2015 Mar 2;12(3):839-45. doi: 10.1021/mp500860x. Epub 2015 Feb 5.

Abstract

Nanobiomaterials such as enveloped virus-like particles with specificity can serve a dual function of vaccination and drug delivery system. Here, we expressed colon carcinoma cell-targeting chimeric virus-like particles (VLPs) made using two capsid proteins, gag and M1 from influenza virus A/swine flu/Iowa/15/30/H1N1 in silkworms. These chimeric VLPs displayed a glycosylphosphatidylinositol-anchored single-chain variable fragment region targeting colon carcinoma cells, and their shape was smooth, with an average particle size of 21 nm in diameter. Large unilamellar vesicles made from DOPC:DOPA (2:1) containing calcein-AM (10 μM) or doxorubicin (13.7 nM) were used to package chimeric VLPs. VLPs showed high specificity in targeting cancer cells and delivered the dye and drug to cells successfully. Chimeric VLPs were injected into BALB/c mice, and the serum showed specificity for M1 protein as a model.

Keywords: chimeric; drug delivery system; silkworm expression system; vaccination; virus-like particles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biopharmaceutics
  • Cell Line, Tumor
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods*
  • Feasibility Studies
  • Female
  • Gene Products, gag / chemistry
  • HEK293 Cells
  • Humans
  • Influenza A Virus, H1N1 Subtype / chemistry
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / immunology
  • Lipid Bilayers / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Particle Size
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / immunology
  • Vaccination / methods*
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / chemistry*
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology

Substances

  • Drug Carriers
  • Gene Products, gag
  • Lipid Bilayers
  • M1 protein, Influenza A virus
  • Single-Chain Antibodies
  • Vaccines, Virus-Like Particle
  • Viral Matrix Proteins