title: Facile preparation of pH-sensitive micelles self-assembled from amphiphilic chondroitin sulfate-histamine conjugate for triggered intracellular drug release.
abstract: Stimuli-responsive materials, enabling drugs to be released in the acidic tumor and intracellular microenvironments, draw an increasing attention in chemotherapy. Here novel pH-sensitive biodegradable micelles are fabricated using a one-step, one-medium process without organic solvent for efficient loading and rapid intracellular release of hydrophobic cargos. The amphiphilic chondroitin sulfate-histamine conjugate (CS-his) were successfully synthesized and assembled into nanoparticles in aqueous medium with desirable size (133 nm) and low critical micelle concentration (CMC) (0.05 mg/L). Owning to the pH-sensitive structure of imidazole, the nanoparticles show pH-responsive behavior upon reducing the pH value of surrounding media, accompany with formation of large aggregates and increase of ζ potential. When the nanoparticles were utilized to deliver the model drug DOX, they exhibited a specific on-off switch drug release behavior, triggering DOX release in acidic surroundings (intracellular endosomes) and sealing DOX in neutral surroundings (blood circulation or extracellular matrix). CCK-8 assays and confocal laser scanning microscopy (CLSM) against HepG2 cells indicated that the nanoparticles themselves had no associated cytotoxicity, while drug-loaded nanoparticles possessed high cytotoxicity to model cells and presented high efficiency of cellular uptake. These flexible micelles with an on-off switched drug release may offer a promising pattern to accurately deliver a wide variety of hydrophobic payloads to tumor cells for cancer therapy.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou University, Lanzhou 730000, People's Republic of China.
authors.forename: Chuanming
authors.initials: C
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou University, Lanzhou 730000, People's Republic of China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou University, Lanzhou 730000, People's Republic of China.
authors.forename: Shaoyu
authors.initials: S
authors.lastname: Lü
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou University, Lanzhou 730000, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou University, Lanzhou 730000, People's Republic of China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Hematology & Oncology, The Second Hospital of Jilin University, Changchun 130041, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Di
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department of Chemistry, Lanzhou University, Lanzhou 730000, People's Republic of China. Electronic address: mzliu@lzu.edu.cn.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Liu
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000138:chemical synthesis / Q000737:chemistry*; D002850:Chromatography, Gel; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006632:Histamine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D012542:Scattering, Radiation; D055672:Static Electricity; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D008823:Micelles; D013501:Surface-Active Agents; D004317:Doxorubicin; D006632:Histamine; D002809:Chondroitin Sulfates
keywords: Chondroitin sulfate; Intracellular drug delivery; Micelles; Self-assembly; pH-responsive