title: pH-dependent, thermosensitive polymeric nanocarriers for drug delivery to solid tumors.
abstract: Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice.
authors.affiliation: Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195-2120, USA.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Tae Hee
authors.initials: TH
authors.lastname: Kim
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Wu
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Wei
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Mount
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Tian
authors.forename: Sei-Hum
authors.initials: SH
authors.lastname: Jang
authors.forename: Suzie H
authors.initials: SH
authors.lastname: Pun
authors.forename: Alex K-Y
authors.initials: AK
authors.lastname: Jen
mesh_terms: D015119:Aminocaproic Acid / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D007267:Injections; D007700:Kinetics; D008027:Light; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D012542:Scattering, Radiation; D013696:Temperature; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; C028914:triethylene glycol; D011092:Polyethylene Glycols; D004317:Doxorubicin; D015119:Aminocaproic Acid