ROS Responsive Nanoplatform with Two-Photon AIE Imaging for Atherosclerosis Diagnosis and "Two-Pronged" Therapy
Boxuan Ma1, Hong Xu1, Weihua Zhuang1
1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China.
Abstract:
Atherosclerosis, characterized by endothelial injury, progressive inflammation, and lipid deposition, can cause cardiovascular diseases. Although conventional anti-inflammatory drugs reveal a certain amount of therapeutic effect, more reasonable design on plaque targeting, local anti-inflammation, and lipid removal are still required for comprehensive atherosclerosis therapy. In this work, a theranostic nanoplatform is developed for atherosclerosis recognition and inhibition. A two-photon aggregation-induced emission (AIE) active fluorophore (TP) developed is linked to β-cyclodextrin (CD) with a ROS responsive bond, which can carry prednisolone (Pred) in its entocoele via supramolecular interaction to build a diagnosis-therapy compound two-photon fluorophore-cyclodextrin/prednisolone complexes (TPCDP). With TPCDP packaged by nanosized micelles based on a ROS sensitive copolymer poly (2-methylthio ethanol methacrylate)-poly (2-methacryloyloxyethyl phosphorylcholine), the TPCDP@PMM can accumulate in atherosclerotic tissue through the damaged vascular endothelium. Activated by the local overexpressed ROS and rich lipid, the micelles are interrupted and TPCDP is further disintegrated with Pred release due to the relatively stronger interaction of lipid with CD, resulting in anti-inflammatory activity and lipid removal for atherosclerosis inhibition. Besides, labeled with the TP, TPCDP@PMM indicates a distinct two-photon AIE imaging on atherosclerosis recognition. The "two-pronged" therapeutic effect and plaque location ability has been confirmed in vivo on ApoE-/- mice, holding TPCDP@PMM a great promise for atherosclerosis theranostics.
Insights
A novel theranostic nanoplatform targets atherosclerosis by combining imaging and therapy. This platform delivers anti-inflammatory drugs and facilitates lipid removal, showing promise for treating cardiovascular disease.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cardiovascular Research
Background:
- Atherosclerosis involves endothelial injury, inflammation, and lipid buildup, leading to cardiovascular diseases.
- Current therapies require improved plaque targeting, local anti-inflammation, and lipid removal strategies.
- Theranostic approaches offer potential for simultaneous diagnosis and treatment of atherosclerosis.
Purpose of the Study:
- To develop a theranostic nanoplatform for atherosclerosis recognition and inhibition.
- To integrate imaging capabilities with targeted drug delivery and therapeutic action.
- To address limitations of conventional treatments by enhancing plaque targeting and local therapeutic effects.
Main Methods:
- A two-photon aggregation-induced emission (AIE) fluorophore (TP) was conjugated to β-cyclodextrin (CD) via a ROS-responsive linker.
- Prednisolone (Pred) was loaded into the CD cavity, forming TPCDP complexes.
- TPCDP was encapsulated within ROS-sensitive micelles (TPCDP@PMM) for targeted delivery.
- In vivo studies were conducted on ApoE-/- mice to evaluate theranostic efficacy.
Main Results:
- TPCDP@PMM accumulated in atherosclerotic tissues via damaged endothelium.
- Local ROS and lipids triggered micelle disruption and Pred release, enabling anti-inflammatory activity and lipid removal.
- The TP component enabled distinct two-photon AIE imaging for atherosclerosis recognition.
- In vivo studies confirmed the dual therapeutic effect and plaque localization capabilities.
Conclusions:
- The developed TPCDP@PMM nanoplatform demonstrates effective atherosclerosis theranostics.
- The system offers targeted drug delivery, local anti-inflammatory action, lipid removal, and in vivo imaging.
- This nanoplatform shows significant promise for the comprehensive management of atherosclerosis.
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