title: pH-Sensitive polymeric micelle-based pH probe for detecting and imaging acidic biological environments.
abstract: To overcome the limitations of monomeric pH probes for acidic tumor environments, this study designed a mixed micelle pH probe composed of polyethylene glycol (PEG)-b-poly(L-histidine) (PHis) and PEG-b-poly(L-lactic acid) (PLLA), which is well-known as an effective antitumor drug carrier. Unlike monomeric histidine and PHis derivatives, the mixed micelles can be structurally destabilized by changes in pH, leading to a better pH sensing system in nuclear magnetic resonance (NMR) techniques. The acidic pH-induced transformation of the mixed micelles allowed pH detection and pH mapping of 0.2-0.3 pH unit differences by pH-induced "on/off"-like sensing of NMR and magnetic resonance spectroscopy. The micellar pH probes sensed pH differences in nonbiological phosphate buffer and biological buffers such as cell culture medium and rat whole blood. In addition, the pH-sensing ability of the mixed micelles was not compromised by loaded doxorubicin. In conclusion, PHis-based micelles could have potential as a tool to simultaneously treat and map the pH of solid tumors in vivo.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah, 421 Wakara Way, Suite 318, Salt Lake City, Utah 84108, USA.
authors.forename: Young Ju
authors.initials: YJ
authors.lastname: Lee
authors.forename: Han Chang
authors.initials: HC
authors.lastname: Kang
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Nichols
authors.forename: Yong Sun
authors.initials: YS
authors.lastname: Jeon
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000494:pharmacology; D004912:Erythrocytes / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008823:Micelles; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000494:pharmacology; D011506:Proteins / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D059016:Tumor Microenvironment
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D007773:Lactates; D008823:Micelles; D015335:Molecular Probes; D011506:Proteins; C088513:poly(lactic acid-ethylene glycol); C480317:polyhistidine-block-polyethylene glycol; D011092:Polyethylene Glycols; D004317:Doxorubicin