Heparin-derived theranostic nanoprobes overcome the blood-brain barrier and target glioma in murine model

Samanta, S.; Le Joncour, V.; Wegrzyniak, O.; Rangasami, V.; Ali-Loytty, H.; Hong, T.; Selvaraju, R. K.; Aberg, O.; Hilborn, J.; Laakkonen, P.; Varghese, O. P.; Eriksson, O.; Cabral, H.; Oommen, O. P.

doi:10.1101/2022.01.07.475195

bioRxiv · 10.1101/2022.01.07.475195

Heparin-derived theranostic nanoprobes overcome the blood-brain barrier and target glioma in murine model

Samanta, S.·Le Joncour, V.·Wegrzyniak, O.·Rangasami, V.·Ali-Loytty, H.·Hong, T.·Selvaraju, R. K.·Aberg, O.·Hilborn, J.·Laakkonen, P.·Varghese, O. P.·Eriksson, O.·Cabral, H.·Oommen, O. P.

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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. We have discovered a new biomimetic nanocarrier using heparin (HP) that effectively passes the BBB and targets glioblastoma. Specifically, we designed HP coated gold nanoparticles (HP-AuNPs) that were 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) displayed excellent penetration and revealed 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 showed 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 display [~]3 fold higher relaxivity than that of commercial Gd-DTPA) in an orthotopic glioblastoma (U87MG xenograft) model in nude mice demonstrated enrichment of T1-contrast at the intracranial tumor with a gradual increase in the contrast in the tumor region between 1h-3h. We believe, our finding offers the untapped potential of HP-derived-NPs to deliver cargo molecules for treating neurological disorders.

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Samanta, S., Le Joncour, V., Wegrzyniak, O., Rangasami, V., Ali-Loytty, H., Hong, T., Selvaraju, R. K., Aberg, O., Hilborn, J., Laakkonen, P., Varghese, O. P., Eriksson, O., Cabral, H., Oommen, O. P.. 2022-01-07. Heparin-derived theranostic nanoprobes overcome the blood-brain barrier and target glioma in murine model. https://doi.org/10.1101/2022.01.07.475195

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