Tumor Targeted Multifunctional Magnetic Nanobubbles for MR/US Dual Imaging and Focused Ultrasound Triggered Drug Delivery
The development of multifunctional nanoplatforms that are safe and have multiple therapeutic functions integrated with dual- or multi-imaging modality is one of the most urgent medical requirements for active cancer therapy. In our study, we prepared multifunctional magnetic nanobubbles (MF-MNBs) by...
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doaj-ef15d1f0127d4f79909a73a7eb9df0f52020-12-08T08:33:48ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-12-01810.3389/fbioe.2020.586874586874Tumor Targeted Multifunctional Magnetic Nanobubbles for MR/US Dual Imaging and Focused Ultrasound Triggered Drug DeliveryZhen Jin0Jinlong Chang1Peipei Dou2Shang Jin3Min Jiao4Heyun Tang5Wenshuai Jiang6Wu Ren7Shaohui Zheng8College of Biomedical Engineering, Xinxiang Medical University, Xinxiang, ChinaCollege of Biomedical Engineering, Xinxiang Medical University, Xinxiang, ChinaSchool of Medical Imaging, Xuzhou Medical University, Xuzhou, ChinaSchool of Medical Imaging, Xuzhou Medical University, Xuzhou, ChinaSchool of Medical Imaging, Xuzhou Medical University, Xuzhou, ChinaSchool of Medical Imaging, Xuzhou Medical University, Xuzhou, ChinaCollege of Biomedical Engineering, Xinxiang Medical University, Xinxiang, ChinaCollege of Biomedical Engineering, Xinxiang Medical University, Xinxiang, ChinaSchool of Medical Imaging, Xuzhou Medical University, Xuzhou, ChinaThe development of multifunctional nanoplatforms that are safe and have multiple therapeutic functions integrated with dual- or multi-imaging modality is one of the most urgent medical requirements for active cancer therapy. In our study, we prepared multifunctional magnetic nanobubbles (MF-MNBs) by co-encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin into polylactideco–glycolide–polyethylene glycol–folate (PLGA-PEG-FA) polymer-based nanobubbles for tumor-targeted ultrasound (US)/magnetic resonance (MR) imaging and focused ultrasound (FUS)-triggered drug delivery. Hydrophobic SPIONs were successfully embedded into MF-MNBs by a typical double emulsion process. The MF-MNBs were highly dispersed with well-defined spherical morphology and an average diameter of 208.4 ± 12.58 nm. The potential of MF-MNB as a dual-modal contrast agent for US and MR imaging was investigated via in vitro study, and the MF-MNB exhibits promising US/MR contrast ability. Moreover, tumor targeting ability was further enhanced by folate conjugation and assessed through in vitro cell test. Furthermore, FUS, as a non-invasive and remote-control technique, was adopted to trigger the release of doxorubicin from MF-MNB and generate the sonoporation effect to enhance drug release and cellular uptake of MF-MNBs. The 4T1 cell viability was significantly decreased by FA ligand-receptor-mediated targeting and FUS sonication. In addition, the developed MF-MNB also exhibits enhanced accumulation in tumor site by FA ligand-receptor-mediated tumor targeting, in which the accumulation of MF-MNB was further enhanced by FUS sonication. Hence, we believe that the MF-MNB could be a promising drug nanocarrier for US/MR-guided anticancer drug delivery to improve cancer treatment efficacy.https://www.frontiersin.org/articles/10.3389/fbioe.2020.586874/fullmultifunctional magnetic nanobubblesUS/MR imagingtumor targetingfocused ultrasound controlled releaseenhanced cellular uptake |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhen Jin Jinlong Chang Peipei Dou Shang Jin Min Jiao Heyun Tang Wenshuai Jiang Wu Ren Shaohui Zheng |
spellingShingle |
Zhen Jin Jinlong Chang Peipei Dou Shang Jin Min Jiao Heyun Tang Wenshuai Jiang Wu Ren Shaohui Zheng Tumor Targeted Multifunctional Magnetic Nanobubbles for MR/US Dual Imaging and Focused Ultrasound Triggered Drug Delivery Frontiers in Bioengineering and Biotechnology multifunctional magnetic nanobubbles US/MR imaging tumor targeting focused ultrasound controlled release enhanced cellular uptake |
author_facet |
Zhen Jin Jinlong Chang Peipei Dou Shang Jin Min Jiao Heyun Tang Wenshuai Jiang Wu Ren Shaohui Zheng |
author_sort |
Zhen Jin |
title |
Tumor Targeted Multifunctional Magnetic Nanobubbles for MR/US Dual Imaging and Focused Ultrasound Triggered Drug Delivery |
title_short |
Tumor Targeted Multifunctional Magnetic Nanobubbles for MR/US Dual Imaging and Focused Ultrasound Triggered Drug Delivery |
title_full |
Tumor Targeted Multifunctional Magnetic Nanobubbles for MR/US Dual Imaging and Focused Ultrasound Triggered Drug Delivery |
title_fullStr |
Tumor Targeted Multifunctional Magnetic Nanobubbles for MR/US Dual Imaging and Focused Ultrasound Triggered Drug Delivery |
title_full_unstemmed |
Tumor Targeted Multifunctional Magnetic Nanobubbles for MR/US Dual Imaging and Focused Ultrasound Triggered Drug Delivery |
title_sort |
tumor targeted multifunctional magnetic nanobubbles for mr/us dual imaging and focused ultrasound triggered drug delivery |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Bioengineering and Biotechnology |
issn |
2296-4185 |
publishDate |
2020-12-01 |
description |
The development of multifunctional nanoplatforms that are safe and have multiple therapeutic functions integrated with dual- or multi-imaging modality is one of the most urgent medical requirements for active cancer therapy. In our study, we prepared multifunctional magnetic nanobubbles (MF-MNBs) by co-encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin into polylactideco–glycolide–polyethylene glycol–folate (PLGA-PEG-FA) polymer-based nanobubbles for tumor-targeted ultrasound (US)/magnetic resonance (MR) imaging and focused ultrasound (FUS)-triggered drug delivery. Hydrophobic SPIONs were successfully embedded into MF-MNBs by a typical double emulsion process. The MF-MNBs were highly dispersed with well-defined spherical morphology and an average diameter of 208.4 ± 12.58 nm. The potential of MF-MNB as a dual-modal contrast agent for US and MR imaging was investigated via in vitro study, and the MF-MNB exhibits promising US/MR contrast ability. Moreover, tumor targeting ability was further enhanced by folate conjugation and assessed through in vitro cell test. Furthermore, FUS, as a non-invasive and remote-control technique, was adopted to trigger the release of doxorubicin from MF-MNB and generate the sonoporation effect to enhance drug release and cellular uptake of MF-MNBs. The 4T1 cell viability was significantly decreased by FA ligand-receptor-mediated targeting and FUS sonication. In addition, the developed MF-MNB also exhibits enhanced accumulation in tumor site by FA ligand-receptor-mediated tumor targeting, in which the accumulation of MF-MNB was further enhanced by FUS sonication. Hence, we believe that the MF-MNB could be a promising drug nanocarrier for US/MR-guided anticancer drug delivery to improve cancer treatment efficacy. |
topic |
multifunctional magnetic nanobubbles US/MR imaging tumor targeting focused ultrasound controlled release enhanced cellular uptake |
url |
https://www.frontiersin.org/articles/10.3389/fbioe.2020.586874/full |
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