期刊
ACS APPLIED MATERIALS & INTERFACES
卷 9, 期 28, 页码 23508-23519出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b06496
关键词
hyaluronic acid conjugate; MRI contrast agents; tumor diagnosis; biodistribution; biodegradability
资金
- International Science and Technology Cooperation Program of China [2015DFE52780]
- National Natural Science Foundation of China [51373104, 51673127, 81361140343, 81621003]
- Chengdu Science and Technology project [2016-GH03-00005-HZ]
- Applied Basic Research Project of Sichuan Province [2015JY0279]
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 HOOC 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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