Reactive Oxygen Species-Responsive Sequentially Targeted AIE Fluorescent Probe for Precisely Identifying the
Jie Liu1, Zhigui He1, Yuan Zhong1
1Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400044, China.
Abstract:
The formation of atherosclerosis is the root cause of various cardiovascular diseases (CVDs). Therefore, effective CVD interventions call for precise identification of the plaques to aid in clinical treatment of such diseases. Herein, a reactive oxygen species (ROS)-responsive sequentially targeted fluorescent probe is developed for atherosclerotic plaque recognition. An aggregation-induced emission active fluorophore is linked to maleimide (polyethylene glycol) hydroxyl with a ROS-responsive cleavable bond, which is further functionalized with CLIKKPF peptide (TPAMCF) for specifically binding to phosphatidylserine of the foam cells. After being assembled in aqueous medium, TPAMCF nanoparticles can efficiently accumulate in the plaques through the high affinity of CLIKKPF to the externalized phosphatidylserine of the foam cells. Activated by the locally accumulated ROS in foam cells, the nanoparticles are interrupted, and then TPA can be released and subsequently identify the lipid droplets inside the foam cells to achieve fluorescence imaging of the plaques. Such nanoprobes have the favorable ROS response performance and exhibit a special target binding to the foam cells in vitro. In addition, nanoprobe-based fluorescence imaging permitted the high-contrast and precise detection of atherosclerosis specimens ex vivo. Therefore, as a promising fluorescent probe, TPAMCF is capable of being a potential candidate for the detection of atherosclerotic plaque.
Insights
A novel fluorescent probe (TPAMCF) precisely identifies atherosclerotic plaques by targeting foam cells and responding to reactive oxygen species (ROS). This allows for high-contrast imaging, aiding cardiovascular disease diagnosis and treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cardiovascular Research
Background:
- Atherosclerosis, a primary cause of cardiovascular diseases (CVDs), necessitates accurate plaque identification for effective clinical intervention.
- Current diagnostic methods require improvement for precise and early detection of atherosclerotic plaques.
Purpose of the Study:
- To develop a reactive oxygen species (ROS)-responsive, sequentially targeted fluorescent probe for specific atherosclerotic plaque recognition.
- To evaluate the probe's efficacy in targeting foam cells and imaging lipid droplets within plaques.
Main Methods:
- A novel probe (TPAMCF) was synthesized, combining an aggregation-induced emission fluorophore with a ROS-cleavable linker and a peptide targeting phosphatidylserine on foam cells.
- The probe was assembled into nanoparticles for aqueous stability and targeted delivery to atherosclerotic plaques.
- In vitro and ex vivo studies were conducted to assess ROS responsiveness, foam cell binding, and fluorescence imaging capabilities.
Main Results:
- TPAMCF nanoparticles demonstrated efficient accumulation in plaques via specific binding to foam cells.
- The probe exhibited favorable ROS responsiveness, releasing its fluorophore upon activation.
- High-contrast and precise fluorescence imaging of atherosclerosis was achieved in ex vivo specimens.
Conclusions:
- The developed TPAMCF probe shows excellent performance in ROS response and specific targeting of foam cells.
- TPAMCF nanoparticles enable high-contrast, precise ex vivo detection of atherosclerotic plaques.
- This fluorescent probe represents a promising candidate for future clinical applications in atherosclerotic plaque detection.
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