β-Cyclodextrin-modified hyaluronic acid-based supramolecular self-assemblies for pH- and esterase- dual-responsive drug delivery

• Published in: Carbohydrate polymers 2020-10, Vol.246, p.116654, Article 116654
• Main Authors: Bai, Yang, Liu, Cai-Ping, Chen, Di, Liu, Cheng-Fei, Zhuo, Long-Hai, Li, Hui, Wang, Chao, Bu, Huai-Tian, Tian, Wei
• Format: Article
• Language: English
• Subjects: A549 Cells; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; beta-Cyclodextrins - chemistry; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cell Line; Cell Survival - drug effects; Cisplatin - analogs & derivatives; Cisplatin - chemistry; Cisplatin - pharmacology; Controlled drug release; Curcumin - chemistry; Curcumin - pharmacology; Delayed-Action Preparations - chemical synthesis; Drug Carriers; Drug Liberation; Esterases - chemistry; Gene Expression; Glycoconjugates - chemistry; Glycoconjugates - pharmacology; Hepatocytes - cytology; Hepatocytes - drug effects; Hepatocytes - metabolism; Host-guest inclusion interaction; Humans; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Hyaluronic Acid - chemistry; Hydrogen-Ion Concentration; Kinetics; Organ Specificity; PC-3 Cells; Stimuli-responsive property; Supramolecular self-assemblies; β-cyclodextrin
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2020.116654

•Host-guest inclusion interactions were utilized to construct active targeting supramolecular self-assembly systems.•Curcumin in Cur-Pt can act as guest molecule included by cyclodextrin.•Supramolecular self-assemblies show pH and esterase dual-responsive co-drug release behaviours. Although some drug-based supramolecular systems have been constructed to overcome multidrug resistance and enhance the bioavailability of chemical drugs, strengthening the specific stimuli-responsive and active targeting ability of these systems is still a major challenge. In this paper, the synthesis and self-assembly behaviour of supramolecular self-assemblies with active targeting β-cyclodextrin-modified hyaluronic acid (HA-CD) and drug-drug conjugates (curcumin-oxoplatin, Cur-Pt) as building moieties were carefully investigated. Notably, the curcumin was chosen not only as the chemical anti-cancer drug, but also acted as the guest molecule which could be included into CD cavity to form host-guest interaction-based supramolecular assemblies. The obtained self-assemblies exhibited pH- and esterase-responsive drug release behaviours. Furthermore, basic cell experiments were performed to prove their effective cellular toxicity based on A549 cells and PC3 cells with high expression of CD44 receptor but they showed no toxicity to normal LO-2 cells with low expression of CD44 receptor, which suggests their potential application in the targeted drug release field.