Heparin-Derived Theranostic Nanoprobes Overcome the Blood–Brain Barrier and Target Glioma in Murine Model

Sumanta Samanta, Vadim Le Joncour, Olivia Wegrzyniak, Vignesh Kumar Rangasami, Harri Ali-Löytty, Taehun Hong, Ram Kumar Selvaraju, Ola Aberg, Jons Hilborn, Pirjo Laakkonen, Oommen P. Varghese, Olof Eriksson, Horacio Cabral, Oommen P. Oommen

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Abstract

The poor permeability of theranostic agents across the blood–brain barrier (BBB) significantly hampers the development of new treatment modalities for neurological diseases. A new biomimetic nanocarrier is discovered using heparin (HP) that effectively passes the BBB and targets glioblastoma. Specifically, HP-coated gold nanoparticles (HP-AuNPs) are designed that are labeled with three different imaging modalities namely, fluorescein (FITC-HP-AuNP), radioisotope 68Gallium (68Ga-HP-AuNPs), and MRI active gadolinium (Gd-HP-AuNPs). The systemic infusion of FITC-HP-AuNPs in three different mouse strains (C57BL/6JRj, FVB, and NMRI-nude) displays excellent penetration and reveals uniform distribution of fluorescent particles in the brain parenchyma (69–86%) with some accumulation in neurons (8–18%) and microglia (4–10%). Tail-vein administration of radiolabeled 68Ga-HP-AuNPs in healthy rats also show 68Ga-HP-AuNP inside the brain parenchyma and in areas containing cerebrospinal fluid, such as the lateral ventricles, the cerebellum, and brain stem. Finally, tail-vein administration of Gd-HP-AuNPs (that displays ≈threefold higher relaxivity than that of commercial Gd-DTPA) in an orthotopic glioblastoma (U87MG xenograft) model in nude mice demonstrates enrichment of T1-contrast at the intracranial tumor with a gradual increase in the contrast in the tumor region between 1 and 3 h. It is believed, the finding offers the untapped potential of HP-derived-NPs to deliver cargo molecules for treating neurological disorders.

Original languageEnglish
Number of pages17
JournalAdvanced Therapeutics
Volume5
Issue number6
DOIs
Publication statusPublished - 2022
Publication typeA1 Journal article-refereed

Keywords

  • blood–brain barriers
  • glioma
  • heparin
  • nanoparticles
  • radioimaging

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Pharmaceutical Science
  • Genetics(clinical)
  • Biochemistry, medical
  • Pharmacology (medical)

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