title: CD44 Receptor Targeting and Endosomal pH-Sensitive Dual Functional Hyaluronic Acid Micelles for Intracellular Paclitaxel Delivery.
abstract: A novel CD44 receptor targeting and endosome pH-sensitive dual functional hyaluronic acid-deoxycholic acid-histidine (HA-DOCA-His) micellar system was designed for intracellular paclitaxel (PTX) delivery. The HA-DOCA-His micelles exhibited desirable endosome pH (5.0-6.0)-induced aggregation and deformation behavior verified by size distribution, critical micellar concentration, and zeta potential changes. The HA-DOCA-His micelles presented excellent encapsulation efficiency and loading capacity of 90.0% and 18.9% for PTX, respectively. The PTX release from HA-DOCA-His micelles was pH-dependent, with more rapid PTX release at pH 6.0 and 5.0 than those at pH 7.4 and 6.5. The cellular uptake performance of HA-DOCA-His micelles was enhanced comparing with pH-insensitive HA-DOCA micelles by qualitative and quantitative measurements. HA-DOCA-His micelles could be taken up via CD44-receptor mediated endocytosis, transported into endosomes, and triggered drug release to cytoplasm. In vitro cytotoxicity study exhibited PTX-loaded HA-DOCA-His micelles were more active in tumor cell growth inhibition in MCF-7 cells at pH 5.8 than those at pH 6.8 and pH 7.4. A superior antitumor efficacy was demonstrated with HA-DOCA-His micelles in a MCF-7 breast tumor model. These indicated that the dual functional HA-DOCA-His micelles combined targeted intracellular delivery and endosomal release strategies could be developed as a promising nanocarrier for anticancer efficacy improvement of PTX.
authors: Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University , No. 1160, Shengli Street, Yinchuan 750004, China.|Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University , Yinchuan 750004, China.
authors: Yanhua
authors: Y
authors: Liu
authors: Department of Pharmacy, Tumor Hospital of General Hospital, Ningxia Medical University , Yinchuan 750004, China.
authors: Chengming
authors: C
authors: Zhou
authors: Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University , No. 1160, Shengli Street, Yinchuan 750004, China.|Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University , Yinchuan 750004, China.
authors: Wenping
authors: W
authors: Wang
authors: Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University , No. 1160, Shengli Street, Yinchuan 750004, China.|Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University , Yinchuan 750004, China.
authors: Jianhong
authors: J
authors: Yang
authors: Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University , No. 1160, Shengli Street, Yinchuan 750004, China.|Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University , Yinchuan 750004, China.
authors: Hao
authors: H
authors: Wang
authors: School of Chemistry and Chemical Engineering, Beifang University of Nationalities , Yinchuan 750021, China.
authors: Wei
authors: W
authors: Hong
authors: Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University , No. 1160, Shengli Street, Yinchuan 750004, China.|Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University , Yinchuan 750004, China.
authors: Yu
authors: Y
authors: Huang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C497483:CD44 protein, human; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D008823:Micelles; D006820:Hyaluronic Acid; D017239:Paclitaxel
keywords: CD44 receptor targeting; HA-DOCA-His micelles; cytosolic PTX delivery; endosomal pH-sensitivity