Fucoidan-Modified Phase-Transitional Contrast Agent for Ultrasound Imaging and Targeting of Hepatoma Cells
Abstract
To prepare a fucoidan-modified phase-transitional contrast agent (FPCA) and to evaluate its in vitro capabilities for ultrasound imaging and targeting of hepatoma cells. Methods Nano-liposomes encapsulated with perfluoropentane were prepared using thin-film hydration and ultrasonic emulsification methods. Then, FPCA nanoparticles were prepared through chemical grafting of fucoidan and the characterization of their physical and chemical properties was performed. After applying external stimuli of heating with hot water bath and microwave irradiation, the phase-transition status of FPCA was observed with microscope. The imaging abilities of phase-transited FPCA on two-dimensional ultrasound and contrast-enhanced ultrasound were observed with ultrasonic diagnostic instrument. The ability of FPCA to target at hepatoma cells was evaluated and verified with fluorescence confocal observation and flow cytometry analysis. Results The FPCA prepared in the study had an average diameter of (222.1±32.5) nm, displaying spherical appearance, good dispersion, good stability, and good biocompatibility. The phase-transition of FPCA was induced by both heating with hot water bath and microwave irradiation. For phase transition, the optimal temperature was found to be 50 ℃ and the preferred microwave power was 1.5 W/cm2. Moreover, after phase transition, FPCA showed significant imaging enhancement on both two-dimensional ultrasonography and contrast-enhanced ultrasonography. Through fluorescein isothiocyanate (FITC) labeling, FPCA could specifically bind with hepatoma cells at a high binding rate of (96.19±1.62)%, while it rarely bound with normal liver cells, showing a binding rate of less than 10%. Conclusion A new type of phase-transitional ultrasound contrast agent with good stability and biocompatibility was successfully prepared. It not only could enhance ultrasound imaging through phase transition, but also had specific active hepatoma cell-targeting properties.
Keywords: Perfluorocarbons, Fucoidan, Phase transition, Targeting, Enhanced ultrasound imaging
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MASSAGUÉ J， BATLLE E， GOMIS R R. Understanding the molecular mechanisms driving metastasis. Mol Oncol，2017，11(1): 3–4. SCHOEN S， KILINC M S， LEE H， et al. Towards controlled drug delivery in brain tumors with microbubble-enhanced focused ultrasound. Adv Drug Delivery Rev， 2022， 180: 114043[2022-02-23]. https://doi.org/ 10.1016/j.addr.2021.114043.
YARMOSKA S K， YOON H， EMELIANOV S Y. Lipid shell composition plays a critical role in the stable size reduction of perfluorocarbon nanodroplets. Ultrasound Med Biol，2019，45(6): 1489–1499.
XU J， CHENG X， TAN L， et al. Microwave responsive nanoplatform via P-selectin mediated drug delivery for treatment of hepatocellular carcinoma with distant metastasis. Nano Letters，2019，19(5): 2914–2927.
KANG R K， MISHR N， RAI V K. Guar Gum micro-particles for targeted co-delivery of doxorubicin and metformin HCL for improved specificity and efficacy against colon cancer: In vitro and in vivo studies. AAPS Pharm Sci Tech，2020，21(2): 48.
YAN M D， LIN H Y， HWANG P A. The anti-tumor activity of brown seaweed oligo-fucoidan via lncRNA expression modulation in HepG2 cells. Cytotechnology，2019，71(1): 363–374.
HE X， XUE M， JIANG S， et al. Fucoidan promotes apoptosis and inhibits EMT of breast cancer cells. Biol Pharm Bull，2019，42(3): 442–447.
DELMA C R， THIRUGNANASAMBANDAN S， SRINIVASAN G P， et al. Fucoidan from marine brown algae attenuates pancreatic cancer progression by regulating p53-NFκB crosstal. Phytochemistry， 2019， 167: 112078[2022-02-23]. https://doi.org/10.1016/j.phytochem.2019.112078.
OLIVEIRA C， NEVES N M， REIS R L， et al. A review on fucoidan antitumor strategies: From a biological active agent to a structural component of fucoidan-based systems. Carbohydr Polym， 2020， 239: 116131[2022-02-23]. https://doi.org/10.1016/j.carbpol.2020.116131.
MABATE B， DAUB C D， MALGAS S， et al. Fucoidan structure and its impact on glucose metabolism: Implications for diabetes and cancer therapy. Marine Drugs，2021，19(1): 30.
AHMAD T， EAPEN M S， ISHAQ M， et al. Anti-inflammatory activity of fucoidan extracts in vitro. Marine Drugs，2021，19(12): 702.
LI S ， LIN S， CHENG Y， et al. Quantifying activation of perfluorocarbon-based phase-change contrast agents using simultaneous acoustic and optical observation. Ultrasound Med Biol，2015，41(5): 1422–1431.
VIDALLON M L P， GILES L W， POTTAGE M J， et al. Tracking the heat-triggered phase change of polydopamine-shelled, perfluorocarbon emulsion droplets into microbubbles using neutron scattering. J Colloid Interface Sci，2022，607: 836–847.
GAO B， XU J， ZHOU J， et al. Multifunctional pathology-mapping theranostic nanoplatforms for US/MR imaging and ultrasound therapy of atherosclerosis. Nanoscale，2021，13(18): 8623–8638.
ZHU Y I， YOON H， ZHAO A X， et al. Leveraging the imaging transmit pulse to manipulate phase-change nanodroplets for contrast-enhanced ultrasound. IEEE Trans Ultrason Ferroelectr Freq Control，2019，66(4): 692–700.
WANG F， WANG Z， PANG L， et al. Preparation and in vitro study of stromal cellderived factor 1targeted Fe3O4/poly(lacticcoglycolic acid)/perfluorohexane nanoparticles. Exp Ther Med，2020，20(3): 2003–2012.
GAO J， YU B， LI C， et al. Ultrasound triggered phase-change nanodroplets for doxorubicin prodrug delivery and ultrasound diagnosis: An in vitro study. Colloids Surf B Biointerfaces，2019，174: 416–425.
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