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  • Title: Gadolinium-Labeled Biodegradable Dendron-Hyaluronic Acid Hybrid and Its Subsequent Application as a Safe and Efficient Magnetic Resonance Imaging Contrast Agent.
    Author: Guo C, Sun L, Cai H, Duan Z, Zhang S, Gong Q, Luo K, Gu Z.
    Journal: ACS Appl Mater Interfaces; 2017 Jul 19; 9(28):23508-23519. PubMed ID: 28656751.
    Abstract:
    Novel magnetic resonance imaging (MRI) contrast agents with high sensitivity and good biocompatibility are required for the diagnosis of cancer. Herein, we prepared and characterized the gadolinium [Gd(III)]-labeled peptide dendron-hyaluronic acid (HA) conjugate-based hybrid (dendronized-HA-DOTA-Gd) by combining the advantages of HA and the peptide dendron. The dendronized-HA-DOTA-Gd hybrid with 3.8% Gd(III) as weight percentage showed a negative zeta potential (-35 mV). The in vitro degradation results indicated that the dendronized-HA-DOTA-Gd hybrid degraded into products with low molecular weights in the presence of hyaluronidase. The dendronized-HA-DOTA-Gd hybrid showed a 3-fold increase in longitudinal relaxivity and much higher in vivo signal enhancement in 4T1 breast tumors of mice compared with clinical Magnevist (Gd-DTPA). The dendronized-HA-DOTA-Gd hybrid had a higher accumulation in tumors than Gd-DTPA; it was 2-3-fold after administration. Meanwhile, the polymeric hybrid resulted in low Gd(III) residue in the body compared with that of Gd-DTPA. The systematic biosafety evaluations, including blood compatibility and toxicity assessments, suggested that the dendronized-HA-DOTA-Gd hybrid exhibited good biocompatibility. Thus, the gadolinium-labeled and dendronized HA hybrid shows promise as a safe and efficient macromolecular MRI contrast agent based on high sensitivity, low residue content in the body, and good biosafety.
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