Heparin-Derived Theranostic Nanoprobes Overcome the Blood–Brain Barrier and Target Glioma in Murine Model
Samanta, Sumanta; Le Joncour, Vadim; Wegrzyniak, Olivia; Rangasami, Vignesh Kumar; Ali-Löytty, Harri; Hong, Taehun; Selvaraju, Ram Kumar; Aberg, Ola; Hilborn, Jons; Laakkonen, Pirjo; Varghese, Oommen P.; Eriksson, Olof; Cabral, Horacio; Oommen, Oommen P. (2022)
Samanta, Sumanta
Le Joncour, Vadim
Wegrzyniak, Olivia
Rangasami, Vignesh Kumar
Ali-Löytty, Harri
Hong, Taehun
Selvaraju, Ram Kumar
Aberg, Ola
Hilborn, Jons
Laakkonen, Pirjo
Varghese, Oommen P.
Eriksson, Olof
Cabral, Horacio
Oommen, Oommen P.
2022
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202204083123
https://urn.fi/URN:NBN:fi:tuni-202204083123
Kuvaus
Peer reviewed
Tiivistelmä
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.
Kokoelmat
- TUNICRIS-julkaisut [16726]