Carbon nanospheres mediated nuclear delivery of SMAR1 protein (DNA binding domain) controls breast tumor in mice model

Nanomedicine (Lond). 2018 Feb;13(4):353-372. doi: 10.2217/nnm-2017-0298. Epub 2018 Jan 17.

Abstract

Aim: To investigate anticancer activity of the DNA binding domain of SMAR1 (His 5) in vitro and in vivo.

Materials & methods: His 5 was conjugated to hydrothermally synthesized carbon nanospheres (CNs). Anticancer activity of CNs-His 5 was evaluated in vitro and in vivo.

Results: CNs- His 5 significantly reduced cyclin D1 levels in MDA-MB-231 cells. Tumor bearing Balb/c mice injected with CNs-His 5 showed approximately 62% tumor regression and significantly reduced 18FDG uptake. Caspases assay and IHC staining confirmed tumor growth inhibition, which could be attributed to apoptotic, antiproliferative and antiangiogenic activities of His 5.

Conclusion: DNA binding domain of the SMAR1 protein (His 5) has potent anticancer activity and its CNs mediated delivery could control breast tumor in mice model.

Keywords: DNA binding domain; PET; SMAR1; breast cancer; carbon nanospheres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Carbon / chemistry*
  • Cell Cycle Proteins / administration & dosage*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclin D1 / metabolism
  • DNA-Binding Proteins / administration & dosage*
  • DNA-Binding Proteins / metabolism
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Female
  • Humans
  • Mice, Inbred BALB C
  • Nanospheres / chemistry*
  • Nuclear Proteins / administration & dosage*
  • Nuclear Proteins / metabolism
  • Protein Domains
  • Recombinant Proteins / administration & dosage
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • BANP protein, human
  • CCND1 protein, human
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Drug Carriers
  • Nuclear Proteins
  • Recombinant Proteins
  • Cyclin D1
  • Carbon