Organosilane and Polyethylene Glycol Functionalized Magnetic Mesoporous Silica Nanoparticles as Carriers for CpG Immunotherapy In Vitro and In Vivo

PLoS One. 2015 Oct 9;10(10):e0140265. doi: 10.1371/journal.pone.0140265. eCollection 2015.

Abstract

Cytosine-guanine (CpG) containing oligodeoxynucleotides (ODN) have significant clinical potential as immunotherapeutics. However, limitations exist due to their transient biological stability in vivo, lack of specificity for target cells, and poor cellular uptake. To address these issues, we prepared amine magnetic mesoporous silica nanoparticles (M-MSN-A) then further modified with polyethylene glycol (PEG) for use as CpG delivery vectors. The PEG modified M-MSN-A (M-MSN-P) had notable CpG ODN loading capacity, negligible cytotoxicity, and were easily internalized into cells where they released the loaded CpG into the cytoplasm. As a result, such complexes were effective in activating macrophages and inhibiting tumor cells when combined with chemotherapeutics in vitro. Furthermore, these complexes had excellent immuno-stimulating activity in vivo, compared to the free CpG therapeutics. We report here a highly effective MSNs-based delivery system with great potential as a therapeutic CpG formulation in cancer immunotherapy.

MeSH terms

  • Adsorption
  • Animals
  • Biological Transport
  • Cell Proliferation
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity
  • HeLa Cells
  • Humans
  • Immunization
  • Immunotherapy*
  • Magnets / chemistry
  • Mice
  • Nanoparticles / chemistry*
  • Oligodeoxyribonucleotides / chemistry*
  • Oligodeoxyribonucleotides / genetics
  • Oligodeoxyribonucleotides / metabolism
  • Polyethylene Glycols / chemistry*
  • Porosity
  • RAW 264.7 Cells
  • Silanes / chemistry*
  • Silicon Dioxide / chemistry*
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CPG-oligonucleotide
  • Drug Carriers
  • Oligodeoxyribonucleotides
  • Silanes
  • Tumor Necrosis Factor-alpha
  • Polyethylene Glycols
  • Silicon Dioxide

Grants and funding

The authors received no specific funding for this work. Qilu Pharmaceutical Co. Ltd. provided support in the form of salary for author S. Wen, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section.