Journal
BIOCONJUGATE CHEMISTRY
Volume 30, Issue 10, Pages 2675-2683Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.9b00587
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Funding
- John S. Dunn Sr. Distinguished Chair Fund in Diagnostic Imaging
- National Institutes of Health (NIH) [P50CA217685, P50CA098258, R35CA209904]
- American Cancer Society Research Professor Award
- Frank McGraw Memorial Chair in Cancer Research
- Ovarian Cancer Research Fund Alliance
- Foundation for Women's Cancer
- Cancer Prevention and Research Institute of Texas [RP101502, RP101489]
- China Postdoctoral Science Foundation [2018M641851]
- Hei Long Jiang Postdoctoral Foundation [LBH-Z18139]
- Cancer Center Support Grant from the National Institutes of Health [P30CA016672]
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Exosomes have attracted tremendous attention due to their important role in physiology, pathology, and oncology, as well as promising potential in biomedical applications. Although great efforts have been dedicated to investigating their biological properties and applications as natural cancer drug-delivery systems, the systemic biodistribution of exosomes remains underexplored. In addition, exosome-based drug delivery is inevitably hindered by the robust liver clearance, leading to suboptimal tumor retention and therapeutic efficiency. In this study, we report one of the first examples using in vivo positron emission tomography (PET) for noninvasive monitoring of copper-64 (Cu-64)-radiolabeled polyethylene glycol (PEG)-modified exosomes, achieving excellent imaging quality and quantitative measurement of blood residence and tumor retention. PEGylation not only endowed exosomes with a superior pharmacokinetic profile and great accumulation in the tumor versus traditionally reported native exosomes but also reduced premature hepatic sequestration and clearance of exosomes, findings that promise enhanced therapeutic delivery efficacy and safety in future studies. More importantly, this study provides important guidelines about surface engineering, radiochemistry, and molecular imaging in obtaining accurate and quantitative biodistribution information on exosomes, which may benefit future exploration in the realm of exosomes.
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