TY - JOUR
T1 - Theranostic Multilayer Capsules for Ultrasound Imaging and Guided Drug Delivery
AU - Chen, Jun
AU - Ratnayaka, Sithira
AU - Alford, Aaron
AU - Kozlovskaya, Veronika
AU - Liu, Fei
AU - Xue, Bing
AU - Hoyt, Kenneth
AU - Kharlampieva, Eugenia
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/3/28
Y1 - 2017/3/28
N2 - 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.
AB - 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.
KW - doxorubicin
KW - drug delivery
KW - hydrogen-bonded
KW - multilayer
KW - tannic acid
KW - ultrasound
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U2 - 10.1021/acsnano.7b00151
DO - 10.1021/acsnano.7b00151
M3 - Article
C2 - 28263564
AN - SCOPUS:85016402327
SN - 1936-0851
VL - 11
SP - 3135
EP - 3146
JO - ACS Nano
JF - ACS Nano
IS - 3
ER -