Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo
Pegylated liposomal doxorubicin (PLD) is a representative nanomedicine that has improved tumor selectivity and safety profile. However, the therapeutic superiority of PLD over conventional doxorubicin has been reported to be insignificant in clinical medicine. Combination treatment with microbubbles...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Drug Delivery |
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| Online Access: | http://dx.doi.org/10.1080/10717544.2021.1895907 |
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| author | Inoru Yokoe Daiki Omata Johan Unga Ryo Suzuki Kazuo Maruyama Yoshiharu Okamoto Tomohiro Osaki |
| author_facet | Inoru Yokoe Daiki Omata Johan Unga Ryo Suzuki Kazuo Maruyama Yoshiharu Okamoto Tomohiro Osaki |
| author_sort | Inoru Yokoe |
| collection | DOAJ |
| description | Pegylated liposomal doxorubicin (PLD) is a representative nanomedicine that has improved tumor selectivity and safety profile. However, the therapeutic superiority of PLD over conventional doxorubicin has been reported to be insignificant in clinical medicine. Combination treatment with microbubbles and ultrasound (US) is a promising strategy for enhancing the antitumor effects of chemotherapeutics by improving drug delivery. Recently, several preclinical studies have shown the drug delivery potential of lipid bubbles (LBs), newly developed monolayer microbubbles, in combination with low-intensity US (LIUS). This study aimed to elucidate whether the combined use of LBs and LIUS enhanced the intratumoral accumulation and antitumor effect of PLD in syngeneic mouse tumor models. Contrast-enhanced US imaging using LBs showed a significant decrease in contrast enhancement after LIUS, indicating that LIUS exposure induced the destruction of LBs in the tumor tissue. A quantitative evaluation revealed that the combined use of LBs and LIUS improved the intratumoral accumulation of PLD. Furthermore, tumor growth was inhibited by combined treatment with PLD, LBs, and LIUS. Therefore, the combined use of LBs and LIUS enhanced the antitumor effect of PLD by increasing its accumulation in the tumor tissue. In conclusion, the present study provides important evidence that the combination of LBs and LIUS is an effective method for enhancing the intratumoral delivery and antitumor effect of PLD in vivo. |
| first_indexed | 2024-12-20T19:02:22Z |
| format | Article |
| id | doaj.art-50dbe3acb5a44f42a24b542ab512aff0 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-12-20T19:02:22Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-50dbe3acb5a44f42a24b542ab512aff02022-12-21T19:29:22ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642021-01-0128153054110.1080/10717544.2021.18959071895907Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivoInoru Yokoe0Daiki Omata1Johan Unga2Ryo Suzuki3Kazuo Maruyama4Yoshiharu Okamoto5Tomohiro Osaki6Faculty of Agriculture, Joint Department of Veterinary Clinical Medicine, Tottori UniversityFaculty of Pharma-Science, Laboratory of Drug and Gene Delivery Research, Teikyo UniversityFaculty of Pharma-Science, Laboratory of Drug and Gene Delivery Research, Teikyo UniversityFaculty of Pharma-Science, Laboratory of Drug and Gene Delivery Research, Teikyo UniversityFaculty of Pharma-Science, Laboratory of Theranostics, Teikyo UniversityFaculty of Agriculture, Joint Department of Veterinary Clinical Medicine, Tottori UniversityFaculty of Agriculture, Joint Department of Veterinary Clinical Medicine, Tottori UniversityPegylated liposomal doxorubicin (PLD) is a representative nanomedicine that has improved tumor selectivity and safety profile. However, the therapeutic superiority of PLD over conventional doxorubicin has been reported to be insignificant in clinical medicine. Combination treatment with microbubbles and ultrasound (US) is a promising strategy for enhancing the antitumor effects of chemotherapeutics by improving drug delivery. Recently, several preclinical studies have shown the drug delivery potential of lipid bubbles (LBs), newly developed monolayer microbubbles, in combination with low-intensity US (LIUS). This study aimed to elucidate whether the combined use of LBs and LIUS enhanced the intratumoral accumulation and antitumor effect of PLD in syngeneic mouse tumor models. Contrast-enhanced US imaging using LBs showed a significant decrease in contrast enhancement after LIUS, indicating that LIUS exposure induced the destruction of LBs in the tumor tissue. A quantitative evaluation revealed that the combined use of LBs and LIUS improved the intratumoral accumulation of PLD. Furthermore, tumor growth was inhibited by combined treatment with PLD, LBs, and LIUS. Therefore, the combined use of LBs and LIUS enhanced the antitumor effect of PLD by increasing its accumulation in the tumor tissue. In conclusion, the present study provides important evidence that the combination of LBs and LIUS is an effective method for enhancing the intratumoral delivery and antitumor effect of PLD in vivo.http://dx.doi.org/10.1080/10717544.2021.1895907pegylated liposomal doxorubicinlipid bubbleslow-intensity ultrasoundsyngeneic mouse tumor modeltumor treatment |
| spellingShingle | Inoru Yokoe Daiki Omata Johan Unga Ryo Suzuki Kazuo Maruyama Yoshiharu Okamoto Tomohiro Osaki Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo Drug Delivery pegylated liposomal doxorubicin lipid bubbles low-intensity ultrasound syngeneic mouse tumor model tumor treatment |
| title | Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo |
| title_full | Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo |
| title_fullStr | Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo |
| title_full_unstemmed | Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo |
| title_short | Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo |
| title_sort | lipid bubbles combined with low intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo |
| topic | pegylated liposomal doxorubicin lipid bubbles low-intensity ultrasound syngeneic mouse tumor model tumor treatment |
| url | http://dx.doi.org/10.1080/10717544.2021.1895907 |
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