Uniform brain tumor distribution and tumor associated macrophage targeting of systemically administered dendrimers

Alessandro Olivi, Fan Zhang, Panagiotis Mastorakos, Manoj K. Mishra, Antonella Mangraviti, Lee Hwang, Jinyuan Zhou, Justin Hanes, Henry Brem, Betty Tyler, Rangaramanujam M. Kannan

Risultato della ricerca: Contributo in rivistaArticolo in rivista

55 Citazioni (Scopus)

Abstract

Effective blood-brain tumor barrier penetration and uniform solid tumor distribution can significantly enhance therapeutic delivery to brain tumors. Hydroxyl-functionalized, generation-4 poly(amidoamine) (PAMAM) dendrimers, with their small size, near-neutral surface charge, and the ability to selectively localize in cells associated with neuroinflammation may offer new opportunities to address these challenges. In this study we characterized the intracranial tumor biodistribution of systemically delivered PAMAM dendrimers in an intracranial rodent gliosarcoma model using fluorescence-based quantification methods and high resolution confocal microscopy. We observed selective and homogeneous distribution of dendrimer throughout the solid tumor (~6mm) and peritumoral area within fifteen minutes after systemic administration, with subsequent accumulation and retention in tumor associated microglia/macrophages (TAMs). Neuroinflammation and TAMs have important growth promoting and pro-invasive effects in brain tumors. The rapid clearance of systemically administered dendrimers from major organs promises minimal off-target adverse effects of conjugated drugs. Therefore, selective delivery of immunomodulatory molecules to TAM, using hydroxyl PAMAM dendrimers, may hold promise for therapy of glioblastoma.
Lingua originaleEnglish
pagine (da-a)507-516
Numero di pagine10
RivistaBiomaterials
Volume52
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • Animals
  • Biodistribution
  • Blood-Brain Barrier
  • Blood-brain barrier
  • Brain Neoplasms
  • Carbocyanines
  • Dendrimers
  • Drug Carriers
  • Drug Delivery Systems
  • Female
  • Glioblastoma
  • Gliosarcoma
  • Inflammation
  • Macrophages
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • PAMAM dendrimer
  • Rats
  • Rats, Inbred F344
  • Tissue Distribution
  • Tumor associated macrophages
  • Tumor penetration

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