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 and Oommen, Oommen P. ORCID: https://orcid.org/0000-0003-2768-0133 2022. Heparin‐derived theranostic nanoprobes overcome the blood–brain barrier and target glioma in murine model. Advanced Therapeutics 5 (6) , 2200001. 10.1002/adtp.202200001

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
ISSN:	2366-3987
Last Modified:	04 Nov 2024 16:30
URI:	https://orca.cardiff.ac.uk/id/eprint/173010

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