title: Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis.
abstract: Tumor therapy requires multi-functional treatment strategies with specific targeting of therapeutics to reduce general toxicity and increase efficacy. In this study we fabricated and functionally tested aptamer-conjugated and doxorubicin (DOX)-loaded acoustic droplets comprising cores of liquid perfluoropentane compound and lipid-based shell materials. Conjugation of sgc8c aptamers provided the ability to specifically target CCRF-CEM cells for both imaging and therapy. High-intensity focused ultrasound (HIFU) was introduced to trigger targeted acoustic droplet vaporization (ADV) which resulted in both mechanical cancer cell destruction by inertial cavitation and chemical treatment through localized drug release. HIFU insonation showed a 56.8% decrease in cell viability with aptamer-conjugated droplets, representing a 4.5-fold increase in comparison to non-conjugated droplets. In addition, the fully-vaporized droplets resulted in the highest DOX uptake by cancer cells, compared to non-vaporized or partially vaporized droplets. Optical studies clearly illustrated the transient changes that occurred upon ADV of droplet-targeted CEM cells, and B-mode ultrasound imaging revealed contrast enhancement by ADV in ultrasound images. In conclusion, our fabricated droplets functioned as a hybrid chemical and mechanical strategy for the specific destruction of cancer cells upon ultrasound-mediated ADV, while simultaneously providing ultrasound imaging capability.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
authors.forename: Chung-Hsin
authors.initials: CH
authors.lastname: Wang
authors.forename: Shih-Tsung
authors.initials: ST
authors.lastname: Kang
authors.forename: Ya-Hsuan
authors.initials: YH
authors.lastname: Lee
authors.forename: Yun-Ling
authors.initials: YL
authors.lastname: Luo
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Huang
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Yeh
mesh_terms: D000162:Acoustics; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004867:Equipment Design; D005466:Fluorocarbons / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry; D009369:Neoplasms / Q000628:therapy*; D013499:Surface Properties; D014464:Ultrasonic Therapy / Q000379:methods*; D014465:Ultrasonics; D010420:Pentanes
chemical_list: D004317:Doxorubicin; D004337:Drug Carriers; D005466:Fluorocarbons; D008055:Lipids; C008806:perfluoropentane; D010420:Pentanes