Targeted drug delivery using genetically engineered diatom biosilica

Nat Commun. 2015 Nov 10:6:8791. doi: 10.1038/ncomms9791.

Abstract

The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in anticancer therapeutics. The use of nanoporous silica-based materials as drug-delivery vehicles has recently proven successful, yet production of these materials requires costly and toxic chemicals. Here we use diatom microalgae-derived nanoporous biosilica to deliver chemotherapeutic drugs to cancer cells. The diatom Thalassiosira pseudonana is genetically engineered to display an IgG-binding domain of protein G on the biosilica surface, enabling attachment of cell-targeting antibodies. Neuroblastoma and B-lymphoma cells are selectively targeted and killed by biosilica displaying specific antibodies sorbed with drug-loaded nanoparticles. Treatment with the same biosilica leads to tumour growth regression in a subcutaneous mouse xenograft model of neuroblastoma. These data indicate that genetically engineered biosilica frustules may be used as versatile 'backpacks' for the targeted delivery of poorly water-soluble anticancer drugs to tumour sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use*
  • Camptothecin / administration & dosage*
  • Camptothecin / therapeutic use*
  • Cell Line, Tumor
  • Cloning, Molecular
  • Diatoms / genetics
  • Diatoms / metabolism*
  • Drug Delivery Systems
  • Gene Expression Regulation
  • Genetic Engineering
  • Immunoglobulin G
  • Liposomes
  • Lymphoma, B-Cell / drug therapy
  • Mice
  • Micelles
  • Nanoparticles
  • Neoplasms, Experimental / drug therapy
  • Neuroblastoma / drug therapy
  • Particle Size
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Silicon Dioxide / metabolism
  • Transplantation, Heterologous

Substances

  • Antibodies
  • Antineoplastic Agents
  • Immunoglobulin G
  • Liposomes
  • Micelles
  • Recombinant Fusion Proteins
  • Silicon Dioxide
  • Camptothecin