Transformation of theranostic alginate-based microbubbles from raspberry-like to core–shell-like microbubbles and in vitro studies

In this study alginate-based microbubbles with a raspberry-like or core–shell-like morphology and with an average particle size of 553.6 ± 69.6 μm were synthesized; this was done through a novel procedure of transforming the structure with a 40 kHz ultrasonication which also stimulated the release of the components inside. Through the use of the electrospray technique in conjunction with agitation processes, components such as shikonin (SHK) and indocyanine green (ICG) were simultaneously encapsulated in alginate microbubbles to produce SHK–ICG alginate microbubbles; these microbubbles had half-maximal inhibitory concentrations of approximately 2.08 and 4.43 μM toward CP70 and SKOV3 ovarian cancer-cell lines, respectively, in an in vitro cell model. Moreover, these SHK–ICG alginate microbubbles enhanced brightness by 2.5 fold in ultrasound imaging relative to CaCl2 medium only. In conclusion, SHK–ICG alginate microbubbles have promise for use in theranostics.

[1]  Yu‐Chi Wang,et al.  Shape‐Controlled Synthesis of Multicomponent‐Encapsulating Alginate Microparticles: Peanut‐, Spherical‐, and Disc‐Shaped Transformations , 2020 .

[2]  O. Yesil‐Celiktas,et al.  One-Step Microfluidic Coating of Phospholipid Microbubbles with Natural Alginate Polymer as a Delivery System for Human Epithelial Lung Adenocarcinoma. , 2020, Macromolecular bioscience.

[3]  J. Eom,et al.  Indocyanine green-loaded injectable alginate hydrogel as a marker for precision cancer surgery. , 2020, Quantitative imaging in medicine and surgery.

[4]  Yu Nie,et al.  Integration of Indocyanine Green Analogs as Near-Infrared Fluorescent Carrier for Precise Imaging-Guided Gene Delivery. , 2020, Small.

[5]  M. Mihai,et al.  The Use of Chitosan, Alginate, and Pectin in the Biomedical and Food Sector—Biocompatibility, Bioadhesiveness, and Biodegradability , 2019, Polymers.

[6]  K. Kang,et al.  Shikonin Exerts Cytotoxic Effects in Human Colon Cancers by Inducing Apoptotic Cell Death via the Endoplasmic Reticulum and Mitochondria-Mediated Pathways , 2018, Biomolecules & therapeutics.

[7]  M. Mokhtari-Dizaji,et al.  Ultrasonic nanotherapy of breast cancer using novel ultrasound-responsive alginate-shelled perfluorohexane nanodroplets: In vitro and in vivo evaluation. , 2017, Materials science & engineering. C, Materials for biological applications.

[8]  Hyuncheol Kim,et al.  Microbubbles used for contrast enhanced ultrasound and theragnosis: a review of principles to applications , 2017, Biomedical Engineering Letters.

[9]  M. Mokhtari-Dizaji,et al.  Novel alginate-stabilized doxorubicin-loaded nanodroplets for ultrasounic theranosis of breast cancer. , 2016, International journal of biological macromolecules.

[10]  Chih-Hui Yang,et al.  A Facile Fabrication of Alginate Microbubbles Using a Gas Foaming Reaction , 2013, Molecules.

[11]  Eleanor Stride,et al.  Calcium Alginate Foams Prepared by a Microfluidic T-Junction System: Stability and Food Applications , 2012, Food and Bioprocess Technology.

[12]  Da-Ren Chen,et al.  Multidrug encapsulation by coaxial tri-capillary electrospray. , 2010, Colloids and surfaces. B, Biointerfaces.

[13]  T. Maehama,et al.  A Naphthoquinone Derivative, Shikonin, Has Insulin-Like Actions by Inhibiting Both Phosphatase and Tensin Homolog Deleted on Chromosome 10 and Tyrosine Phosphatases , 2006, Molecular Pharmacology.

[14]  Nico de Jong,et al.  Ultrasound-induced microbubble coalescence. , 2004, Ultrasound in medicine & biology.

[15]  G Van Camp,et al.  Destruction of Contrast Microbubbles by Ultrasound: Effects on Myocardial Function, Coronary Perfusion Pressure, and Microvascular Integrity , 2001, Circulation.

[16]  M. Edirisinghe,et al.  Bioinspired preparation of alginate nanoparticles using microbubble bursting. , 2015, Materials science & engineering. C, Materials for biological applications.