title: A pH-sensitive micelle composed of heparin, phospholipids, and histidine as the carrier of photosensitizers: Application to enhance photodynamic therapy of cancer.
abstract: In this study, we describe the synthesis of a stable, pH-sensitive micelle composed of heparin, 1, 2-distearoyl-sn-glycerol-3-phosphoethanolamine, and l-histidine (HDH) through 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) chemistry.1H-Nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) analyses confirmed the formation of HDH copolymers and dynamic light scattering (DLS) measurements indicated a particle size of 111.57±12.36nm and zeta potential of -59.8±5.2mV for the nanoparticles. The drug-loading and encapsulation efficiency of the micelles were 14.52±1.2% and 65.47±1.87%, respectively. Drug release studies showed approximately 91% zinc phthalocyanine (ZnPc) release from micelles in acidic conditions (pH 5.0) in comparison with 63% in physiological conditions (pH 7.4) after 96h of incubation. Singlet oxygen (1O2) detection revealed that the micelles prevented ZnPc aggregation and enhanced1O2generation. Cellular uptake of ZnPc-loaded micelles (ZnPc-HDH) was observed using confocal microscopy. Phototoxicity experiments in HeLa cells showed that ZnPc-loaded micelles had higher toxicity than that shown by the same concentration of free ZnPc. Hence, pH-sensitive HDH micelles are a promising carrier for hydrophobic ZnPc and improving PDT efficacy.
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Postcode 106, Taipei, Taiwan.
authors.forename: Tilahun Ayane
authors.initials: TA
authors.lastname: Debele
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Postcode 106, Taipei, Taiwan.
authors.forename: Shewaye Lakew
authors.initials: SL
authors.lastname: Mekuria
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Postcode 106, Taipei, Taiwan. Electronic address: h.c.tsai@mail.ntust.edu.tw.
authors.forename: Hsieh-Chih
authors.initials: HC
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001692:Biological Transport; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D006367:HeLa Cells; D006493:Heparin / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D054833:Isoindoles; D008823:Micelles; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010743:Phospholipids / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D026082:Singlet Oxygen / Q000378:metabolism; D013552:Swine; D017967:Zinc Compounds
chemical_list: D004337:Drug Carriers; D007211:Indoles; D054833:Isoindoles; D008823:Micelles; D009942:Organometallic Compounds; D010743:Phospholipids; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D026082:Singlet Oxygen; D006639:Histidine; D006493:Heparin
keywords: Heparin; Micelles; Phospholipid; Photodynamic therapy; Zinc phthalocyanine