Star-polymer unimolecular micelle nanoparticles to deliver a payload across the blood-brain barrier

Nanoscale. 2024 Nov 28;16(46):21582-21593. doi: 10.1039/d4nr02636e.

Abstract

Nanocarrier-mediated therapeutic delivery to brain tissue is impeded by tightly controlled transportation across the blood-brain barrier (BBB). Herein, we report a well-defined core-shell star-shaped unimolecular micelle (star-UMM; a single polymer entity) as an efficient BBB-breaching nanoparticle for brain-specific administration of the fluorescent anticancer drug doxorubicin and in vivo mapping of brain tissues by the near-infrared biomarker IR780 in mice. The star-UMM was engineered by precisely programming the polymer topology having hydrophobic and hydrophilic polycaprolactone blocks and in-built with lysosomal enzyme-biodegradation stimuli to deliver the payloads at intracellular compartments. In vivo imaging in mice revealed prolonged circulation of star-UMM in blood for >72 h, and whole-organ image-quantification substantiated its efficient ability to breach the BBB. Star UMM exhibited excellent stability in blood circulation and reduced cardiotoxicity, was non-hemolytic, had substantial uptake in the cortical neurons of the mouse brain, had lysosomal enzymatic-biodegradation, and exhibited negligible immunogenicity or necrosis. This newly designed star-UMM could have long-term applications in brain-specific drug delivery.

MeSH terms

  • Animals
  • Blood-Brain Barrier* / metabolism
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacokinetics
  • Doxorubicin* / pharmacology
  • Drug Carriers* / chemistry
  • Drug Delivery Systems
  • Humans
  • Indoles / chemistry
  • Mice
  • Micelles*
  • Nanoparticles* / chemistry
  • Polyesters* / chemistry
  • Polymers / chemistry

Substances

  • Micelles
  • Doxorubicin
  • Drug Carriers
  • Polyesters
  • polycaprolactone
  • Indoles
  • Polymers
  • 2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium