Journal
ACS NANO
Volume 15, Issue 9, Pages 14509-14521Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c04029
Keywords
nanoprobes; drug delivery; microbubbles; apoptosis detection; molecular imaging
Categories
Funding
- National Key R&D Program of China [2018YFC0115900, 2020YFA0908800]
- National Natural Science Foundation of China [81871376, 81660381]
- Guangdong Innovation Platform of Translational Research for Cerebrovascular Diseases
- Shenzhen Science and Technology Innovation Committee [JCYJ20190812171820731, JCYJ20170412171856582, ZDSYS201802061806314]
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Focused ultrasound combined with microbubbles is a potential approach to open the blood-brain barrier for drug delivery. Nanoprobe-loaded MBs can monitor cell apoptotic events during this process, providing a new strategy for treating brain diseases.
Focused ultrasound (FUS) combined with microbubbles (MBs) has recently emerged as a potential approach to open the blood-brain barrier (BBB) for delivering drugs into the brain. However, appropriate approaches are still lacking to monitor the sublethal damage during FUS-mediated BBB opening in vivo, especially the early stage cell apoptotic events. Here, we developed a kind of nanoprobe-loaded MBs (AV-ICG-NPs@MBs) which can monitor the apoptotic cells that occur during FUS-mediated BBB opening through encapsulating the annexin V-targeted nanoprobes AV-ICG-NPs into the cavity of lipid-PLGA hybrid MBs. When irradiated by FUS, AV-ICG-NPs@MBs in the cerebral blood vessels would produce cavitation, favoring the BBB opening. Meanwhile, AV-ICG-NPs@MBs would be destroyed and release their AV-ICG-NPs payload. These released AV-ICG-NPs can be further delivered into the brain via the destructed BBB and bind with the phosphatidylserine externalized on the membrane of apoptotic cells if this occurs, leading to the prolonged detention of fluorescent signals in the brain. Furthermore, we also provided an effective strategy to inhibit or reverse the possible damage to the brain from a FUS-mediated BBB opening technology, through developing AV-ICG-NPs/GAS@MBs that encapsulate the antioxidant gastrodin (GAS) into AV-ICGNPs@MBs. Accompanied by FUS irradiation and bubble cavitation, GAS was released and delivered into the brain, where they scavenged the oxygen free radicals produced from cavitation, leading to significantly lower fluorescence signals in the brain due to the absence of externalized phosphatidylserine. In conclusion, our study provides an approach to monitor and inhibit cell apoptotic events during FUS-mediated BBB opening.
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