title: Design of novel multifunctional targeting nano-carrier drug delivery system based on CD44 receptor and tumor microenvironment pH condition.
abstract: In this study, to develop a multifunctional targeting nano-carrier drug delivery system for cancer therapy, the novel pH-sensitive ketal based oligosaccharides of hyaluronan (oHA) conjugates were synthesized by chemical conjugation of hydrophobic menthone 1,2-glycerol ketal (MGK) to the backbone of oHA with the histidine as the linker of proton sponge effect. The multifunctional oHA conjugates, oHA-histidine-MGK (oHM) carried the pH-sensitive MGK as hydrophobic moieties and oHA as the target of CD44 receptor. The oHM could self-assemble to nano-sized spherical shape with the average diameters of 128.6 nm at pH 7.4 PBS conditions. The oHM nanoparticles (oHMN) could release encapsulated curcumin (Cur) with 82.6% at pH 5.0 compared with 49.3% at pH 7.4. The results of cytotoxicity assay indicated that encapsulated Cur in oHMN (Cur-oHMN) were stable and have less toxicity compared to Cur suspension. The anti-tumor efficacy in vivo suggested that Cur-oHMN suppressed tumor growth most efficiently. These results present the promising potential of oHMN as a stable and effective nano-sized pH-sensitive drug delivery system for cancer treatment.
authors.affiliation: a School of Pharmacy, Yantai University , Yantai , People's Republic of China .
authors.forename: Daquan
authors.initials: D
authors.lastname: Chen
authors.affiliation: a School of Pharmacy, Yantai University , Yantai , People's Republic of China .
authors.forename: Shengnan
authors.initials: S
authors.lastname: Lian
authors.affiliation: a School of Pharmacy, Yantai University , Yantai , People's Republic of China .
authors.forename: Jingfang
authors.initials: J
authors.lastname: Sun
authors.affiliation: a School of Pharmacy, Yantai University , Yantai , People's Republic of China .
authors.forename: Zongliang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: a School of Pharmacy, Yantai University , Yantai , People's Republic of China .
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: a School of Pharmacy, Yantai University , Yantai , People's Republic of China .|b State Key Laboratory of Long-acting and Targeting Drug Delivery System , Yantai , People's Republic of China , and.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: c College of Pharmacy, University of Georgia , Athens , GA , USA.
authors.forename: Mingming
authors.initials: M
authors.lastname: Gao
authors.affiliation: a School of Pharmacy, Yantai University , Yantai , People's Republic of China .|b State Key Laboratory of Long-acting and Targeting Drug Delivery System , Yantai , People's Republic of China , and.
authors.forename: Kaoxiang
authors.initials: K
authors.lastname: Sun
authors.affiliation: a School of Pharmacy, Yantai University , Yantai , People's Republic of China .|b State Key Laboratory of Long-acting and Targeting Drug Delivery System , Yantai , People's Republic of China , and.
authors.forename: Wanhui
authors.initials: W
authors.lastname: Liu
authors.affiliation: a School of Pharmacy, Yantai University , Yantai , People's Republic of China .|b State Key Laboratory of Long-acting and Targeting Drug Delivery System , Yantai , People's Republic of China , and.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Fu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; C476399:Cd44 protein, mouse; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D011108:Polymers; D006820:Hyaluronic Acid; D003474:Curcumin
keywords: 2-glycerol ketal (oHM); Drug delivery; nanoparticles; oHA-histidine– menthone 1; oligosaccharides of hyaluronan (oHA); pH-sensitive