Autor: |
Andreas Tue Ingemann Jensen, Jonas Rosager Henriksen, Johan Tham, Anders Elias Hansen, Daniella Elisabet Østergaard, Andreas Kjaer, Anne Skovsbo Clausen, Peter Damborg, Petter Holmberg, Thomas Lars Andresen |
Rok vydání: |
2021 |
Předmět: |
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Zdroj: |
Journal of Controlled Release. 330:976 |
ISSN: |
0168-3659 |
DOI: |
10.1016/j.jconrel.2020.11.004 |
Popis: |
Background Therapeutic interventions for infectious and inflammatory diseases are becoming increasingly challenging in terms of therapeutic resistance and side-effects. Theranostic systems to ameliorate diagnosis and therapy are therefore highly warranted. The pathophysiological changes in inflammatory lesions provide an attractive basis for extravasation and accumulation of PEGylated liposomes. The objective of this study was to provide direct quantitative information on the theranostic potential of radiolabeled liposome for accumulation in inflammatory models using position emission tomography (PET). Method Preclinical murine models of inflammation (turpentine and LPS), infection (Staphylococcus aureus) and collagen-induced arthritis (CIA) was established and monitored using bioluminescence imaging (BLI). Across all models PET imaging using radiolabeled PEGylated liposomes (64Cu-liposomes) were performed and evaluated in terms of accumulation properties in inflammatory and infectious lesions. Results BLI demonstrated that the inflammatory and infectious models were successfully established and provided information on lesion pathology. Activity of 64Cu-liposomes were increased in inflammatory and infectious lesions between early (10-min or 3-h) and late (24-h) PET scans, which validates that a continuous extravasation and accumulation of long circulation PEGylated liposomes occurs. Conclusion The theranostic potential of long circulating PEGylated radiolabeled liposomes was shown in multiple preclinical models. Impressive accumulation was seen in both inflammatory and infectious lesions. These results are encouraging towards advancing PEGylated liposomes as imaging and drug delivery systems in inflammatory and infectious diseases. |
Databáze: |
OpenAIRE |
Externí odkaz: |
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