Liver-Specific and Echogenic Hyaluronic Acid Nanoparticles Facilitating Liver Cancer Discrimination
- Liver-Specific and Echogenic Hyaluronic Acid Nanoparticles Facilitating Liver Cancer Discrimination
- 민현수; 손세진; 이태웅; 구희범; 윤홍열; 나진희; 최용석; 박재형; 이재용; 한문희; 박랑운; 김인산; 정서영; 이계한; 김선화; 권익찬; 김광명
- ultrasound imaging; ultrasound contrast agents; hyaluronic acid (HA); perfluoropentane (PFP); liver-targeting treatments
- Issue Date
- Advanced functional materials
- VOL 23, NO 44, 5518-5529
- With the increasing demand for instant real-time ultrasound (US) imaging of a specific organ, target-specific and long-circulating ultrasound contrast agents are of special interest. A new species of echogenic hyaluronic acid nanoparticles is presented as an ultralong-acting, liver-specific, US contrast agent that is distinct from conventional gas-filled microbubbles. Using an oil-in-water (O/W) emulsification method, bioinert and hydrophobic perfluoropentane (PFP) is encapsulated as an ultrasound gas precursor into hyaluronic acid nanoparticles (HANPs) using hydrophobic interactions. HANPs are formulated by self-assembly, with amphiphilic hyaluronic acid-5β-cholanic acid (HA-CA) conjugating in aqueous conditions. The resulting echogenic PFP-encapsulated HANPs (Echo-NPs) show solid nanostructures, differentiated from core-empty conventional microbubbles, and exhibiting outstanding physical properties as an ultrasound contrast agent. They are more stable and robust echogenic solid bodies with an in vivo favorable hydrodynamic size and because PFPs vaporize gradually, their expansion process is very slow in body conditions. After several systemic circulations, echo-NPs generated intense and ultralong echo signals for US imaging at the target site. The echogenic properties of Echo-NPs show a significantly increased half-life and echo persistence, compared with conventional microbubbles. The results clearly show that echo-NPs outperform conventional microbubbles in terms of both physical and echogenic in vitro and in vivo properties.
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