Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes
Objective: Thermosensitive liposomal doxorubicin (TSL–Dox) is a promising stimuli-responsive nanoparticle drug delivery system that rapidly releases the contained drug in response to hyperthermia (HT) (>40 °C). Combined with localized heating, TSL–Dox allows highly localized delivery. The goals o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | International Journal of Hyperthermia |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/02656736.2019.1642521 |
| _version_ | 1819023154834571264 |
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| author | Anjan Motamarry Ayele H. Negussie Christian Rossmann James Small A. Marissa Wolfe Bradford J. Wood Dieter Haemmerich |
| author_facet | Anjan Motamarry Ayele H. Negussie Christian Rossmann James Small A. Marissa Wolfe Bradford J. Wood Dieter Haemmerich |
| author_sort | Anjan Motamarry |
| collection | DOAJ |
| description | Objective: Thermosensitive liposomal doxorubicin (TSL–Dox) is a promising stimuli-responsive nanoparticle drug delivery system that rapidly releases the contained drug in response to hyperthermia (HT) (>40 °C). Combined with localized heating, TSL–Dox allows highly localized delivery. The goals of this study were to demonstrate that real-time fluorescence imaging can visualize drug uptake during delivery, and can predict tumor drug uptake. Methods: Nude mice carrying subcutaneous tumors (Lewis lung carcinoma) were anesthetized and injected with TSL–Dox (5 mg/kg dose). Localized HT was induced by heating tumors for 15, 30 or 60 min via a custom-designed HT probe placed superficially at the tumor location. In vivo fluorescence imaging (excitation 523 nm, emission 610 nm) was performed before, during, and for 5 min following HT. After imaging, tumors were extracted, drug uptake was quantified by high-performance liquid chromatography, and correlated with in vivo fluorescence. Plasma samples were obtained before and after HT to measure TSL–Dox pharmacokinetics. Results: Local drug uptake could be visualized in real-time during HT. Compared to unheated control tumors, fluorescence of heated tumors increased by 4.6-fold (15 min HT), 9.3-fold (30 min HT), and 13.2-fold (60 min HT). HT duration predicted tumor drug uptake (p = .02), with tumor drug concentrations of 4.2 ± 1.3 µg/g (no HT), 7.1 ± 5.9 µg/g (15 min HT), 14.1 ± 6.7 µg/g (30 min HT) and 21.4 ± 12.6 µg/g (60 min HT). There was good correlation (R2 = 0.67) between fluorescence of the tumor region and tumor drug uptake. Conclusions: Real-time in vivo fluorescence imaging can visualize drug uptake during delivery, and can predict tumor drug uptake. |
| first_indexed | 2024-12-21T04:34:23Z |
| format | Article |
| id | doaj.art-b93222ca05f94f0298ec0be2af4c7cde |
| institution | Directory Open Access Journal |
| issn | 0265-6736 1464-5157 |
| language | English |
| last_indexed | 2024-12-21T04:34:23Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | International Journal of Hyperthermia |
| spelling | doaj.art-b93222ca05f94f0298ec0be2af4c7cde2022-12-21T19:15:53ZengTaylor & Francis GroupInternational Journal of Hyperthermia0265-67361464-51572019-01-0136181682510.1080/02656736.2019.16425211642521Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomesAnjan Motamarry0Ayele H. Negussie1Christian Rossmann2James Small3A. Marissa Wolfe4Bradford J. Wood5Dieter Haemmerich6Medical University of South CarolinaNational Institutes of HealthMedical University of South CarolinaMedical University of South CarolinaMedical University of South CarolinaNational Institutes of HealthMedical University of South CarolinaObjective: Thermosensitive liposomal doxorubicin (TSL–Dox) is a promising stimuli-responsive nanoparticle drug delivery system that rapidly releases the contained drug in response to hyperthermia (HT) (>40 °C). Combined with localized heating, TSL–Dox allows highly localized delivery. The goals of this study were to demonstrate that real-time fluorescence imaging can visualize drug uptake during delivery, and can predict tumor drug uptake. Methods: Nude mice carrying subcutaneous tumors (Lewis lung carcinoma) were anesthetized and injected with TSL–Dox (5 mg/kg dose). Localized HT was induced by heating tumors for 15, 30 or 60 min via a custom-designed HT probe placed superficially at the tumor location. In vivo fluorescence imaging (excitation 523 nm, emission 610 nm) was performed before, during, and for 5 min following HT. After imaging, tumors were extracted, drug uptake was quantified by high-performance liquid chromatography, and correlated with in vivo fluorescence. Plasma samples were obtained before and after HT to measure TSL–Dox pharmacokinetics. Results: Local drug uptake could be visualized in real-time during HT. Compared to unheated control tumors, fluorescence of heated tumors increased by 4.6-fold (15 min HT), 9.3-fold (30 min HT), and 13.2-fold (60 min HT). HT duration predicted tumor drug uptake (p = .02), with tumor drug concentrations of 4.2 ± 1.3 µg/g (no HT), 7.1 ± 5.9 µg/g (15 min HT), 14.1 ± 6.7 µg/g (30 min HT) and 21.4 ± 12.6 µg/g (60 min HT). There was good correlation (R2 = 0.67) between fluorescence of the tumor region and tumor drug uptake. Conclusions: Real-time in vivo fluorescence imaging can visualize drug uptake during delivery, and can predict tumor drug uptake.http://dx.doi.org/10.1080/02656736.2019.1642521hyperthermiacancerdrug delivery systemsthermosensitive liposomeschemotherapyliposomes |
| spellingShingle | Anjan Motamarry Ayele H. Negussie Christian Rossmann James Small A. Marissa Wolfe Bradford J. Wood Dieter Haemmerich Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes International Journal of Hyperthermia hyperthermia cancer drug delivery systems thermosensitive liposomes chemotherapy liposomes |
| title | Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes |
| title_full | Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes |
| title_fullStr | Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes |
| title_full_unstemmed | Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes |
| title_short | Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes |
| title_sort | real time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes |
| topic | hyperthermia cancer drug delivery systems thermosensitive liposomes chemotherapy liposomes |
| url | http://dx.doi.org/10.1080/02656736.2019.1642521 |
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