Hyaluronic Acid-Based Nanogel–Drug Conjugates with Enhanced Anticancer Activity Designed for the Targeting of CD44-Positive and Drug-Resistant Tumors
作者： Xin Wei , Thulani H. Senanayake , Galya Warren , Serguei V. Vinogradov
DOI: 10.1021/BC300632W
关键词: Cytotoxicity 、 Pharmacology 、 Glycoprotein binding 、 Curcumin 、 Nanogel 、 Chemistry 、 Cancer stem cell 、 Drug 、 Etoposide 、 Hyaluronic acid 、 Biochemistry
摘要: Many drug-resistant tumors and cancer stem cells (CSC) express elevated levels of CD44 receptor, a cellular glycoprotein binding hyaluronic acid (HA). Here, we report the synthesis nanogel–drug conjugates based on membranotropic cholesteryl-HA (CHA) for efficient targeting suppression tumors. These significantly increased bioavailability poorly soluble drugs with previously reported activity against CSC, such as etoposide, salinomycin, curcumin. The small nanogel particles (diameter 20–40 nm) hydrophobic core high drug loads (up to 20%) formed after ultrasonication demonstrated sustained release following hydrolysis biodegradable ester linkage. Importantly, CHA–drug nanogels 2–7 times higher cytotoxicity in CD44-expressing human breast pancreatic adenocarcinoma compared that free nonmodified HA–drug conjugates. were efficiently internalized via receptor-medi...
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