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Development of Micro/Nanobubbles for Theranostic Applications.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Development of Micro/Nanobubbles for Theranostic Applications./
Author:	Song, Ruyuan.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
Description:	149 p.
Notes:	Source: Dissertations Abstracts International, Volume: 82-03, Section: B.
Contained By:	Dissertations Abstracts International82-03B.
Subject:	Bioengineering. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28176532
ISBN:	9798664749533

Development of Micro/Nanobubbles for Theranostic Applications.
Song, Ruyuan.

Development of Micro/Nanobubbles for Theranostic Applications. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 149 p.

Source: Dissertations Abstracts International, Volume: 82-03, Section: B.

Thesis (Ph.D.)--Hong Kong University of Science and Technology (Hong Kong), 2018.

Micro/nanobubbles have been widely developed as theranostics for a variety of biomedical applications, such as contrast ultrasound imaging, cancer detection, and imaging-guided drug delivery. The sonoporation and the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles offer extra benefits for drug delivery. Besides, micro/nanobubbles hold great potential to overcome hypoxia in solid tumors which significantly compromises therapeutic outcomes. However, current microbubbles suffer from the stability issues and polydispersed populations which still limit their applications in imaging and therapy. Therefore, monodisperse and stable micro/nanobubbles are still highly desired. First, we develop a microfluidic flow focusing approach to produce monodisperse microbubbles stabilized by poly (lactic-co-glycolic acid) as the polymer shell. The size and size distribution of polymer microbubbles can be tightly controlled for ensuring highly homogeneous echogenic behavior of the bubbles in ultrasound fields. Both in vitro and in vivo experiments showed that the monodisperse polymer microbubbles had excellent echogenicity and elongated sonographic duration time (> 3 times) for ultrasound imaging in comparison with the commercial lipid microbubbles. Second, we designed an ultrasound-responsive stable oxygen microbubble to sensitize hypoxic areas in solid tumors for the brachytherapy. A modified emulsion freeze-drying method was developed to prepare microbubbles that could be lyophilized for storage and easily reconstituted in situ before administration. The filling gases of the microbubbles were modified by addition of sulfur hexafluoride into oxygen so that the obtained microbubbles achieved ~3 times higher in half-life time and greatly enhanced ultrasound contrast. The post-treatment results of the brachytherapy combined with ultrasound-triggered microbubbles revealed ~1.15 times decrease in tumor growth rate, compared to the brachytherapy alone, manifesting ultrasound-mediated oxygen delivery with oxygen microbubbles as a promising strategy to improve the therapeutic outcome of the brachytherapy on hypoxic tumors. Besides, we developed a lipid-polymer bilaminar oxygen nanobubble with chlorin e6 (Ce6) conjugated to the polymer shell as a novel self-oxygen supplement photodynamic therapy (PDT) platform. The resultant nanobubbles showed excellent stability to reduce risk of premature oxygen release and were stored as freeze-dried powders to avoid shelf storage issues. In vitro and in vivo experimental results demonstrated that the nanobubbles exhibited much higher cellular uptake rate and tumor targeting efficiency compared to free Ce6. Using the oxygen nanobubbles for PDT, a significant enhancement of therapeutic efficacy and survival rates was manifested on C6 glioma tumors with no noticeable side effect thanks to the greatly enhanced single oxygen generation powered by oxygen encapsulated in nanobubbles. This thesis presents novel fabrication methods of monodisperse microbubbles and exploits the application of micro/nanobubbles to tackle the hypoxia in the solid tumors which haunts many therapeutic modules. We believe our work surely has shed new light on the treatment of tumors with improved therapeutic outcomes.

ISBN: 9798664749533Subjects--Topical Terms:

657580
Bioengineering.
Subjects--Index Terms:

Micro/nanobubbles

Development of Micro/Nanobubbles for Theranostic Applications.
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245 1 0 $a Development of Micro/Nanobubbles for Theranostic Applications.
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300 $a 149 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-03, Section: B.
500 $a Advisor: Yao, Shuhuai.
502 $a Thesis (Ph.D.)--Hong Kong University of Science and Technology (Hong Kong), 2018.
520 $a Micro/nanobubbles have been widely developed as theranostics for a variety of biomedical applications, such as contrast ultrasound imaging, cancer detection, and imaging-guided drug delivery. The sonoporation and the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles offer extra benefits for drug delivery. Besides, micro/nanobubbles hold great potential to overcome hypoxia in solid tumors which significantly compromises therapeutic outcomes. However, current microbubbles suffer from the stability issues and polydispersed populations which still limit their applications in imaging and therapy. Therefore, monodisperse and stable micro/nanobubbles are still highly desired. First, we develop a microfluidic flow focusing approach to produce monodisperse microbubbles stabilized by poly (lactic-co-glycolic acid) as the polymer shell. The size and size distribution of polymer microbubbles can be tightly controlled for ensuring highly homogeneous echogenic behavior of the bubbles in ultrasound fields. Both in vitro and in vivo experiments showed that the monodisperse polymer microbubbles had excellent echogenicity and elongated sonographic duration time (> 3 times) for ultrasound imaging in comparison with the commercial lipid microbubbles. Second, we designed an ultrasound-responsive stable oxygen microbubble to sensitize hypoxic areas in solid tumors for the brachytherapy. A modified emulsion freeze-drying method was developed to prepare microbubbles that could be lyophilized for storage and easily reconstituted in situ before administration. The filling gases of the microbubbles were modified by addition of sulfur hexafluoride into oxygen so that the obtained microbubbles achieved ~3 times higher in half-life time and greatly enhanced ultrasound contrast. The post-treatment results of the brachytherapy combined with ultrasound-triggered microbubbles revealed ~1.15 times decrease in tumor growth rate, compared to the brachytherapy alone, manifesting ultrasound-mediated oxygen delivery with oxygen microbubbles as a promising strategy to improve the therapeutic outcome of the brachytherapy on hypoxic tumors. Besides, we developed a lipid-polymer bilaminar oxygen nanobubble with chlorin e6 (Ce6) conjugated to the polymer shell as a novel self-oxygen supplement photodynamic therapy (PDT) platform. The resultant nanobubbles showed excellent stability to reduce risk of premature oxygen release and were stored as freeze-dried powders to avoid shelf storage issues. In vitro and in vivo experimental results demonstrated that the nanobubbles exhibited much higher cellular uptake rate and tumor targeting efficiency compared to free Ce6. Using the oxygen nanobubbles for PDT, a significant enhancement of therapeutic efficacy and survival rates was manifested on C6 glioma tumors with no noticeable side effect thanks to the greatly enhanced single oxygen generation powered by oxygen encapsulated in nanobubbles. This thesis presents novel fabrication methods of monodisperse microbubbles and exploits the application of micro/nanobubbles to tackle the hypoxia in the solid tumors which haunts many therapeutic modules. We believe our work surely has shed new light on the treatment of tumors with improved therapeutic outcomes.
590 $a School code: 1223.
650 4 $a Bioengineering. $3 657580
650 4 $a Nanoscience. $3 587832
653 $a Micro/nanobubbles
653 $a Theranostic
690 $a 0565
690 $a 0202
710 2 $a Hong Kong University of Science and Technology (Hong Kong). $3 1022235
773 0 $t Dissertations Abstracts International $g 82-03B.
790 $a 1223
791 $a Ph.D.
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793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28176532