Theranostic hyaluronic acid prodrug micelles with aggregation- induced emission characteristics for targeted drug delivery  

作　　者：Lin Wang Haoke Zhang Anjun Qin Qiao Jin Ben Zhong Tang Jian Ji 

机构地区：[1]Key Laboratory of Macromolecular Synthesis and Functionalization, Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China [2]State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640, China [3]Department of Chemistry, The Hong Kong University of Science ＆ Technology, Kowloon, Hong Kong, China

出　　处：《Science China Chemistry》2016年第12期1609-1615,共7页中国科学（化学英文版）

基　　金：supported by the Key Science Technology Innovation Team of Zhejiang Province(2013TD02);the National Natural Science Foundation of China(51303154,51573160,21574114);the Fundamental Research Funds for the Central Universities(2016QNA4033)

摘　　要：Theranostic hyaluronic acid(HA) prodrug micelles with pH-responsive drug release and aggregation-induced emission(AIE)properties were prepared by chemical graft of biomimetic phosphorylcholine(PC), anticancer drug doxorubicin(DOX) and AIE fluorogen tetraphenylene(TPE) to the HA backbone. DOX was conjugated to the HA backbone by a hydrazone bond which can be hydrolyzed under acidic environment and result in pH-triggered smart release of DOX. The TPE units with typical AIE characteristics were applied for real time drug tracking in cancer cells. The HA-based prodrugs could self-assemble into micelles in aqueous solution as confirmed by the dynamic light scattering(DLS) and transmission electron microscopy(TEM). The intracellular distribution of HA prodrug micelles could be clearly observed by fluorescence microscopy based on the strong fluorescence of TPE. Moreover, after treated with the micelles, stronger fluorescence of TPE in CD44 overexpressed MDA-MB-231 cancer cells was observed, compared to the CD44 negative cell line, NIH3T3 cells, suggesting efficient cell uptake of HA prodrug micelles by receptor-mediated endocytosis. The cell viability results indicated that the prodrug micelles could inhibit the proliferation of the cancer cells effectively. Such pH-triggered theranostic drug delivery system with AIE features can provide a new platform for targeted and image-guided cancer therapy.Theranostic hyaluronic acid （HA） prodrug micelles with pH-responsive drug release and aggregation-induced emission （AIE） properties were prepared by chemical graft of biomimetic phosphorylcholine （PC）, anticancer drug doxorubicin （DOX） and AIE fluorogen tetraphenylene （TPE） to the HA backbone. DOX was conjugated to the HA backbone by a hydrazone bond which can be hydrolyzed under acidic environment and result in pH-triggered smart release of DOX. The TPE units with typi- cal AIE characteristics were applied for real time drug tracking in cancer cells. The HA-based prodrugs could self-assemble into micelles in aqueous solution as confirmed by the dynamic light scattering （DLS） and transmission electron microscopy （TEM）. The intracellular distribution of HA prodrug micelles could be clearly observed by fluorescence microscopy based on the strong fluorescence of TPE. Moreover, after treated with the micelles, stronger fluorescence of TPE in CD44 over- expressed MDA-MB-231 cancer cells was observed, compared to the CD44 negative cell line, NIH3T3 cells, suggesting effi- cient cell uptake of HA prodrug micelles by receptor-mediated endocytosis. The cell viability results indicated that the prodrug micelles could inhibit the proliferation of the cancer cells effectively. Such pH-triggered theranostic drug delivery system with AIE features can provide a new platform for targeted and image-guided cancer therapy.

关 键 词：hyaluronic acid AIE PRODRUG drug delivery 

分 类 号：TQ460.1[化学工程—制药化工]