MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications

Nanomedicine. 2017 Nov;13(8):2495-2505. doi: 10.1016/j.nano.2017.08.006. Epub 2017 Aug 24.

Abstract

Mucin 1 (MUC1) is a cell surface protein overexpressed in breast cancer. Mesoporous silica nanoparticles (MSNs) loaded with safranin O, functionalized with aminopropyl groups and gated with the negatively charged MUC1 aptamer have been prepared (S1-apMUC1) for specific targeting and cargo release in tumoral versus non-tumoral cells. Confocal microscopy studies showed that the S1-apMUC1 nanoparticles were internalized in MDA-MB-231 breast cancer cells that overexpress MUC1 receptor with subsequent pore opening and cargo release. Interestingly, the MCF-10-A non-tumorigenic breast epithelial cell line that do not overexpress MUC1, showed reduced (S1-apMUC1) internalization. Negligible internalization was also found for S1-ap nanoparticles that contained a scrambled DNA sequence as gatekeeper. S2-apMUC1 nanoparticles (similar to S1-apMUC1 but loaded with doxorubicin) internalized in MDA-MB-231 cells and induced a remarkable reduction in cell viability. Moreover, S1-apMUC1 nanoparticles radio-labeled with 99mTc (S1-apMUC1-Tc) showed a remarkable tumor targeting in in vivo studies with MDA-MB-231 tumor-bearing Balb/c mice.

Keywords: Mesoporous silica nanoparticles; Nanotechnology; Oncology; Radiopharmaceuticals.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Aptamers, Nucleotide / metabolism*
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Delayed-Action Preparations / metabolism*
  • Female
  • Humans
  • Mice, Inbred BALB C
  • Mucin-1 / analysis
  • Mucin-1 / metabolism*
  • Nanoparticles / metabolism*
  • Phenazines / administration & dosage*
  • Phenazines / therapeutic use
  • Porosity
  • Silicon Dioxide / metabolism*
  • Theranostic Nanomedicine

Substances

  • Antineoplastic Agents
  • Aptamers, Nucleotide
  • Delayed-Action Preparations
  • MUC1 protein, human
  • Mucin-1
  • Phenazines
  • Silicon Dioxide
  • safranine T