期刊
COLLOIDS AND SURFACES B-BIOINTERFACES
卷 198, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.colsurfb.2020.111455
关键词
pH-responsive; Hyaluronic acid; Curcumin; CD44 receptor; Enhanced cancer therapy
资金
- National Natural Science Foundation of China [81302715/H3008]
In this study, amphiphilic HA-ADH-CUR conjugates were synthesized and self-assembled to form HA@CUR NPs which exhibited pH-responsive drug release behavior. The nanoparticles could efficiently internalize by cancer cells via CD44 receptor mediated endocytosis and release CUR for chemotherapy, showing promising potential for enhanced cancer therapy.
Curcumin (CUR) display promising antitumor effects, however, the poor water solubility severely limited its clinical application. To overcome this problem, polymeric nanocarriers have been adopted for targeted CUR delivery and enhanced cancer therapy. In this paper, utilizing an acid-labile hydrazone linkage, hydrophobic CUR was conjugated with hydrophilic hyalumnic acid (HA) to form amphiphilic HA-ADH-CUR conjugates, which could subsequently self-assemble to form nanoparticles (HA@CUR NPs) in aqueous. The in vitro drug release experiments showed that HA@CUR NPs exhibited a pH-responsive CUR release behavior, and the release rate of CUR was 73.5 % in pH 5.0. Further, in vitro cell experiments showed HA@CUR NPs could be efficiently internalized by 4T1 and MCF-7 cancer cells through CD44 receptor mediated endocytosis and successfully release CUR in acidic lysosome environment for chemotherapy. In vivo antitumor experiments showed that, compared to free CUR, HA@CUR NPs could efficiently cumulate in tumor site via EPR effect and CD44 mediated endocytosis, achieve superior therapeutic effect for tumor growth suppression. Therefore, HA@CUR NPs were a highly promising nanocarrier for hydrophobic CUR to realize enhanced cancer therapy with good biosafety.
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