First in vivo MRI study on theranostic dendrimersomes

J Control Release. 2017 Feb 28:248:45-52. doi: 10.1016/j.jconrel.2017.01.010. Epub 2017 Jan 7.

Abstract

Amphiphilic Janus-dendrimers are able to self-assemble into nanosized vesicles named dendrimersomes. We recently synthesized the 3,5-C12-EG-(OH)4 dendrimer that generates dendrimersomes with very promising safety and stability profiles, that can be loaded with different contrast agents for in vivo imaging. In this contribution, nanovesicles were loaded with both the Magnetic Resonance Imaging (MRI) reporter GdDOTAGA(C18)2 and the glucocorticoid drug Prednisolone Phosphate (PLP), in order to test their effective potential as theranostic nanocarriers on murine melanoma tumour models. The incorporation of GdDOTAGA(C18)2 into the membrane resulted in dendrimersomes with a high longitudinal relaxivity (r1=39.1mM-1s-1, at 310K and 40MHz) so that, after intravenous administration, T1-weighted MRI showed a consistent contrast enhancement in the tumour area. Furthermore, the nanovesicles encapsulated PLP with good efficiency and displayed anti-tumour activity both in vitro and in vivo, thus enabling their practical use for biomedical theranostic applications.

Keywords: Dendrimersomes; Magnetic Resonance Imaging; Melanoma; Prednisolone Phosphate; Theranostic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Contrast Media / administration & dosage*
  • Contrast Media / pharmacokinetics
  • Dendrimers / chemistry*
  • Female
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / pharmacokinetics
  • Heterocyclic Compounds / administration & dosage*
  • Heterocyclic Compounds / pharmacokinetics
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Melanoma / diagnostic imaging*
  • Melanoma / drug therapy
  • Mice
  • Mice, Inbred C57BL
  • Nanocapsules / chemistry*
  • Organometallic Compounds / administration & dosage*
  • Organometallic Compounds / pharmacokinetics
  • Prednisolone / administration & dosage
  • Prednisolone / analogs & derivatives*
  • Prednisolone / pharmacokinetics
  • Theranostic Nanomedicine

Substances

  • Contrast Media
  • Dendrimers
  • Glucocorticoids
  • Heterocyclic Compounds
  • Nanocapsules
  • Organometallic Compounds
  • prednisolone phosphate
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
  • Prednisolone