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Ma, Guanglong, Kostevšek, Nina, Monaco, Ilaria, Ruiz, Amalia, Markelc, Boštjan, Cheung, Calvin C. l., Hudoklin, Samo, Kreft, Mateja E., Hassan, Hatem A. F. M., Barker, Matthew, Conyard, Jamie, Hall, Christopher, Meech, Stephen 
ORCID: https://orcid.org/0000-0001-5561-2782, Mayes, Andrew G., Serša, Igor, Čemažar, Maja, Marković, Katarina, Ščančar, Janez, Franchini, Mauro Comes and Al-Jamal, Wafa T.
(2021)
PD1 blockade potentiates the therapeutic efficacy of photothermally-activated and MRI-guided low temperature-sensitive magnetoliposomes.
Journal of Controlled Release, 332.
pp. 419-433.
ISSN 0168-3659
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Abstract
This study investigates the effect of PD1 blockade on the therapeutic efficacy of novel doxorubicin-loaded temperature-sensitive liposomes. Herein, we report photothermally-activated, low temperature-sensitive magnetoliposomes (mLTSL) for efficient drug delivery and magnetic resonance imaging (MRI). The mLTSL were prepared by embedding small nitrodopamine palmitate (NDPM)-coated iron oxide nanoparticles (IO NPs) in the lipid bilayer of low temperature-sensitive liposomes (LTSL), using lipid film hydration and extrusion. Doxorubicin (DOX)-loaded mLTSL were characterized using dynamic light scattering, differential scanning calorimetry, electron microscopy, spectrofluorimetry, and atomic absorption spectroscopy. Photothermal experiments using 808 nm laser irradiation were conducted. In vitro photothermal DOX release studies and cytotoxicity was assessed using flow cytometry and resazurin viability assay, respectively. In vivo DOX release and tumor accumulation of mLTSL(DOX) were assessed using fluorescence and MR imaging, respectively. Finally, the therapeutic efficacy of PD1 blockade in combination with photothermally-activated mLTSL(DOX) in CT26-tumor model was evaluated by monitoring tumor growth, cytokine release and immune cell infiltration in the tumor tissue. Interestingly, efficient photothermal heating was obtained by varying the IO NPs content and the laser power, where on-demand burst DOX release was achievable in vitro and in vivo. Moreover, our mLTSL exhibited promising MR imaging properties with high transverse r 2 relaxivity (333 mM −1 s −1), resulting in superior MR imaging in vivo. Furthermore, mLTSL(DOX) therapeutic efficacy was potentiated in combination with anti-PD1 mAb, resulting in a significant reduction in CT26 tumor growth via immune cell activation. Our study highlights the potential of combining PD1 blockade with mLTSL(DOX), where the latter could facilitate chemo/photothermal therapy and MRI-guided drug delivery.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | anti-pd1,iron oxide nanoparticles,magnetoliposomes,photothermal,theranostics,thermosensitive,pharmaceutical science ,/dk/atira/pure/subjectarea/asjc/3000/3003 |
| Faculty \ School: | Faculty of Science > School of Pharmacy Faculty of Science > School of Chemistry |
| UEA Research Groups: | Faculty of Science > Research Groups > Chemistry of Light and Energy Faculty of Science > Research Groups > Chemistry of Materials and Catalysis Faculty of Science > Research Groups > Centre for Photonics and Quantum Science |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 15 May 2021 00:12 |
| Last Modified: | 09 Feb 2023 13:49 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/80022 |
| DOI: | 10.1016/j.jconrel.2021.03.002 |
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