title: Tumor-targeting hyaluronic acid nanoparticles for photodynamic imaging and therapy.
abstract: Tumor-targeted imaging and therapy have been the challenging issue in the clinical field. Herein, we report tumor-targeting hyaluronic acid nanoparticles (HANPs) as the carrier of the hydrophobic photosensitizer, chlorin e6 (Ce6) for simultaneous photodynamic imaging and therapy. First, self-assembled HANPs were synthesized by chemical conjugation of aminated 5β-cholanic acid, polyethylene glycol (PEG), and black hole quencher3 (BHQ3) to the HA polymers. Second, Ce6 was readily loaded into the HANPs by a simple dialysis method resulting in Ce6-loaded hyaluronic acid nanoparticles (Ce6-HANPs), wherein in the loading efficiency of Ce6 was higher than 80%. The resulting Ce6-HANPs showed stable nano-structure in aqueous condition and rapid uptake into tumor cells. In particular Ce6-HANPs were rapidly degraded by hyaluronidases abundant in cytosol of tumor cells, which may enable intracellular release of Ce6 at the tumor tissue. After an intravenous injection into the tumor-bearing mice, Ce6-HANPs could efficiently reach the tumor tissue via the passive targeting mechanism and specifically enter tumor cells through the receptor-mediated endocytosis based on the interactions between HA of nanoparticles and CD44, the HA receptor on the surface of tumor cells. Upon laser irradiation, Ce6 which was released from the nanoparticles could generate fluorescence and singlet oxygen inside tumor cells, resulting in effective suppression of tumor growth. Overall, it was demonstrated that Ce6-HANPs could be successfully applied to in vivo photodynamic tumor imaging and therapy simultaneously.
authors.affiliation: Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hong Yeol
authors.initials: HY
authors.lastname: Yoon
authors.forename: Heebeom
authors.initials: H
authors.lastname: Koo
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Choi
authors.forename: So Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: James F
authors.initials: JF
authors.lastname: Leary
authors.forename: Kinam
authors.initials: K
authors.lastname: Park
authors.forename: Soon Hong
authors.initials: SH
authors.lastname: Yuk
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002735:Chlorophyllides; D003952:Diagnostic Imaging / Q000379:methods*; D005453:Fluorescence; D019073:HT29 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D011166:Porphyrins / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D026082:Singlet Oxygen / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared
chemical_list: D002735:Chlorophyllides; D011166:Porphyrins; D026082:Singlet Oxygen; C062985:phytochlorin; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase