ROS Responsive Nanoplatform with Two‐Photon AIE Imaging for Atherosclerosis Diagnosis and “Two‐Pronged” Therapy

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.

Recent Advances in ROS-Sensitive Nano-Formulations for Atherosclerosis Applications

“…Moreover, an improved nano-platform with simultaneous response to the high concentration of ROS and enriched lipids at the atherosclerosis site was developed. By conjugating TP to β-cyclodextrin carrying prednisolone, the compound TPCDP was synthesized, and it was then packaged into PMM to obtained TPCDP@PMM [ 120 ]. The in vivo bioimaging of TPCDP@PMM on ApoE −/− mice showed efficient accumulation in atherosclerosis tissue and clear plaque recognition.…”

“…The in vivo bioimaging of TPCDP@PMM on ApoE −/− mice showed efficient accumulation in atherosclerosis tissue and clear plaque recognition. In addition, the development of atherosclerotic plaques was effectively inhibited by the “two-pronged” anti-inflammatory and lipid removal approach, revealing their great potential for atherosclerosis theranostic applications [ 120 ].…”

Practicable Applications of Aggregation‐Induced Emission with Biomedical Perspective

“…Following this work, they used a similar idea to construct therapeutic micelles for atherosclerosis. [114] In addition to the same imaging with two-photon AIE molecules and treatment with Pred as before, the 𝛽-cyclodextrin (CD) used to load and link the ROS response bonds also have a lipid scavenging effect, making the treatment of atherosclerosis more effective (Figure 17e,f).…”

ROS-Based Nanoparticles for Atherosclerosis Treatment

“…ROS-responsive NPs are developed to release drugs only at the target sites which generate excess ROS. Through this, these NPs could contribute to both improving treatment efficiency and reducing adverse side effects [53,54,67,[83][84][85][86][87][88]. In consideration of the excess ROS level in an abnormal organization, many ROS-sensitive materials, including polythioether ketal, ketone mercaptan, ferrocene and selenium-containing copolymers, have been explored [52,57].…”

“…In addition, the sites overexpressing ROS can be used as targets for directed delivery of therapeutic agents and accurate fluorescence diagnosis. Furthermore, Ma et al constructed therapeutic NPs (TPP) with continuous ROS responsiveness and two-photon AIE bioimaging for multimodal diagnosis and precise treatment of the lesions of excess ROS [53,84]. Prednisolone was connected to the two-photon fluorophore through ROS-sensitive bonds to form the diagnostic and therapeutic compound TPP, then loaded by the amphiphilic polymer self-assembled into a core-shell structured micelle (Figure 8) [53].…”