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

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Samanta , S , Le Joncour , V , Wegrzyniak , O , Rangasami , V K , 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 , ' Heparin-Derived Theranostic Nanoprobes Overcome the Blood-Brain Barrier and Target Glioma in Murine Model ' , Advanced Therapeutics , vol. 5 , no. 6 , 2200001 . https://doi.org/10.1002/adtp.202200001

Title: Heparin-Derived Theranostic Nanoprobes Overcome the Blood-Brain Barrier and Target Glioma in Murine Model
Author: Samanta, Sumanta; Le Joncour, Vadim; Wegrzyniak, Olivia; Rangasami, Vignesh Kumar; Ali-Loytty, Harri; Hong, Taehun; Selvaraju, Ram Kumar; Aberg, Ola; Hilborn, Jons; Laakkonen, Pirjo; Varghese, Oommen P.; Eriksson, Olof; Cabral, Horacio; Oommen, Oommen P.
Contributor organization: CAN-PRO - Translational Cancer Medicine Program
Helsinki Institute of Life Science HiLIFE, Infra
Pirjo Maarit Laakkonen / Principal Investigator
Biosciences
Date: 2022-06
Language: eng
Number of pages: 17
Belongs to series: Advanced Therapeutics
ISSN: 2366-3987
DOI: https://doi.org/10.1002/adtp.202200001
URI: http://hdl.handle.net/10138/345726
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 (68)Gallium (Ga-68-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 Ga-68-HP-AuNPs in healthy rats also show Ga-68-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 approximate to 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.
Subject: blood-brain barriers
glioma
heparin
nanoparticles
radioimaging
COATED GOLD NANOPARTICLES
MOLECULAR-WEIGHT HEPARIN
DRUG-DELIVERY
CONTRAST AGENTS
BINDING
OLIGOSACCHARIDES
NANOLIPOSOMES
ENOXAPARIN
LIPOSOMES
CONSTANTS
317 Pharmacy
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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