title: Development of multifunctional hyaluronan-coated nanoparticles for imaging and drug delivery to cancer cells.
abstract: Currently, there is high interest in developing multifunctional theranostic platforms for cancer monitoring and chemotherapy. Herein, we report hyaluronan (HA)-coated superparamagnetic iron oxide nanoparticles (HA-SPION) as a promising system for targeted imaging and drug delivery. When incubated with cancer cells, HA-SPIONs were rapidly taken up and the internalization of HA-SPION by cancer cells was much higher than the NPs without HA coating. The high magnetic relaxivity of HA-SPION coupled with enhanced uptake enabled magnetic resonance imaging of cancer cells. Furthermore, doxorubicin (DOX) was attached onto the nanoparticles through an acid responsive linker. While HA-SPION was not toxic to cells, DOX-HA-SPION was much more potent than free DOX to kill not only drug-sensitive but also multi-drug-resistant cancer cells. This was attributed to differential uptake mechanisms and cellular distributions of free DOX and DOX-HA-SPION in cancer cells.
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, United States.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: El-Dakdouki
authors.forename: David C
authors.initials: DC
authors.lastname: Zhu
authors.forename: Kheireddine
authors.initials: K
authors.lastname: El-Boubbou
authors.forename: Medha
authors.initials: M
authors.lastname: Kamat
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xuefei
authors.initials: X
authors.lastname: Huang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology*; D003952:Diagnostic Imaging; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D018613:Microscopy, Confocal; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D020099:Coated Materials, Biocompatible; D004317:Doxorubicin; D006820:Hyaluronic Acid