3 years ago

Gadolinium-Labeled Biodegradable Dendron–Hyaluronic Acid Hybrid and Its Subsequent Application as a Safe and Efficient Magnetic Resonance Imaging Contrast Agent

Gadolinium-Labeled Biodegradable Dendron–Hyaluronic Acid Hybrid and Its Subsequent Application as a Safe and Efficient Magnetic Resonance Imaging Contrast Agent
Kui Luo, Chunhua Guo, Ling Sun, Zhongwei Gu, Hao Cai, Qiyong Gong, Shiyong Zhang, Zhenyu Duan
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.

Publisher URL: http://dx.doi.org/10.1021/acsami.7b06496

DOI: 10.1021/acsami.7b06496

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