title: Theranostic Multilayer Capsules for Ultrasound Imaging and Guided Drug Delivery.
abstract: Despite the accessibility of ultrasound, the clinical potential of ultrasound-active theranostic agents has not been fully realized because it requires combining sufficient imaging contrast, high encapsulation efficiency, and ultrasound-triggered release in one entity. We report on theranostic polymer microcapsules composed of hydrogen-bonded multilayers of tannic acid and poly(N-vinylpyrrolidone) that produce high imaging contrast and deliver the anticancer drug doxorubicin upon low-power diagnostic or high-power therapeutic ultrasound irradiation. These capsules exhibit excellent imaging contrast in both brightness and harmonic modes and show prolonged contrast over six months, unlike commercially available microbubbles. We also demonstrate low-dose gradual and high-dose fast release of doxorubicin from the capsules by diagnostic (∼100 mW/cm2) and therapeutic (>10 W/cm2) ultrasound irradiation, respectively. We show that the imaging contrast of the capsules can be controlled by varying the number of layers, polymer type (relatively rigid tannic acid versus more flexible poly(methacrylic acid)), and polymer molecular weight. In vitro studies demonstrate that 50% doxorubicin release from ultrasound-treated capsules induces 97% cytotoxicity to MCF-7 human cancer cells, while no cytotoxicity is found without the treatment. Considering the strong ultrasound imaging contrast, high encapsulation efficiency, biocompatibility, and tunable drug release, these microcapsules can be used as theranostic agents for ultrasound-guided chemotherapy.
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
authors.forename: Sithira
authors.initials: S
authors.lastname: Ratnayaka
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
authors.forename: Aaron
authors.initials: A
authors.lastname: Alford
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
authors.forename: Veronika
authors.initials: V
authors.lastname: Kozlovskaya
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
authors.forename: Bing
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department of Bioengineering, University of Texas at Dallas , Richardson, Texas 75080, United States.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hoyt
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
authors.forename: Eugenia
authors.identifier: 0000-0003-0227-0920
authors.initials: E
authors.lastname: Kharlampieva
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D002214:Capsules / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D061848:Optical Imaging; D010316:Particle Size; D016062:Porosity; D011205:Povidone / Q000737:chemistry; D013329:Structure-Activity Relationship; D013634:Tannins / Q000737:chemistry; D000068936:Theranostic Nanomedicine; D014465:Ultrasonics
chemical_list: D000903:Antibiotics, Antineoplastic; D002214:Capsules; D003287:Contrast Media; D004337:Drug Carriers; D013634:Tannins; D004317:Doxorubicin; D011205:Povidone
keywords: doxorubicin; drug delivery; hydrogen-bonded; multilayer; tannic acid; ultrasound