title: Reduction/pH dual-sensitive PEGylated hyaluronan nanoparticles for targeted doxorubicin delivery.
abstract: To minimize the side effect of chemotherapy, a novel reduction/pH dual-sensitive drug nanocarrier, based on PEGylated dithiodipropionate dihydrazide (TPH)-modified hyaluronic acid (PEG-SS-HA copolymer), was developed for targeted delivery of doxorubicin (DOX) to hepatocellular carcinoma. The copolymer was synthesized by reductive amination via Schiff's base formation between TPH-modified HA and galactosamine-conjugated poly(ethylene glycol) aldehyde/methoxy poly(ethylene glycol) aldehyde. Conjugation of DOX to PEG-SS-HA copolymer was accomplished through the hydrazone linkage formed between DOX and PEG-SS-HA, and confirmed by FTIR and (1)H NMR spectra. The polymer-DOX conjugate could self-assemble into spherical nanoparticles (~150 nm), as indicated by TEM and DLS. In vitro release studies showed that the DOX-loaded nanoparticles could release DOX rapidly under the intracellular levels of pH and glutathiose. Cellular uptake experiments demonstrated that the nanoparticles could be efficiently internalized by HepG2 cells. These results indicate that the PEG-SS-HA copolymer holds great potential for targeted intracellular delivery of DOX.
authors.affiliation: State Key Laboratory for Mechanical Behaviors of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Xu
authors.forename: Junmin
authors.initials: J
authors.lastname: Qian
authors.forename: Aili
authors.initials: A
authors.lastname: Suo
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wang
authors.forename: Xueqing
authors.initials: X
authors.lastname: Yong
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Liu
authors.forename: Rongrong
authors.initials: R
authors.lastname: Liu
mesh_terms: D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis; D005688:Galactosamine / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000737:chemistry*; D011422:Propionates / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D011422:Propionates; C013298:thiodipropionic acid; D011092:Polyethylene Glycols; D005688:Galactosamine; D004317:Doxorubicin; D006820:Hyaluronic Acid
keywords: Doxorubicin; Hyaluronic acid; Nanoparticle; PEGylation; Reduction/pH dual-sensitivity; Targeted drug delivery