Recent advances of self-assembled nanoparticles in the diagnosis and treatment of atherosclerosis

Abstract

Atherosclerosis remains a significant global health challenge, with its related conditions as the leading cause of death, underscoring the urgent need for enhanced diagnostic and therapeutic approaches. Recently, self-assembled nanoparticles (SANPs) have shown remarkable promise in treating atherosclerosis, attributed to their superior bioavailability, biodegradability, biocompatibility, and ease of functional modification. Numerous SANP variants, such as DNA origami, metal-organic frameworks (MOFs), nanozymes, peptide-based nanoparticles, and self-assembled prodrug nanoparticles, have been engineered, extending their utility in targeted drug delivery and imaging. Advances in fabrication technologies, including microfluidic techniques, allow for precise and scalable SANP production, while innovative nanoparticle designs-such as stimuli-responsive and carrier-free variants-enhance pharmacokinetic properties. The deployment of SANPs in atherosclerosis has introduced a range of diagnostic and therapeutic solutions, from non-invasive imaging and stimuli-responsive drug delivery to vaccination, theranostics, and biosensing. This review consolidates the recent progress in SANP applications for atherosclerosis, emphasizing their transformative potential in disease management.

Keywords: atherosclerosis; diagnosis; nanoparticles; self-assembled nanoparticles; treatment.

Figure 1

Schematic for SANPs based strategies for diagnosis and treatment of atherosclerosis. Created by Figdraw.

Figure 2

Schematic illustrations for new preparation methods and design strategies for developing self-assembled nanoparticles. A. Schematic illustration for preparing RNA-loaded lipid nanoparticles using microfluidic device. Reproduced with permission from . Copyright 2022, Elsevier. B. Schematic illustrations of stimuli responsive nanoparticles and various stimuli employed for controlled drug release. Reproduced with permission from . Copyright 2014, John Wiley and Sons.

Figure 3

Self-assembled nanoparticles for atherosclerosis non-invasive imaging. A. Schematic illustration of ratiometric photoacoustic semiconducting polymer nanoparticles (RSPNs) for in vivo imaging of atherosclerotic plaques. RSPNs respond to superoxide anions (O₂⁻), enhancing the photoacoustic signal at 690 nm with 800 nm as a reference, enabling specific detection of oxidative stress within plaques. Reproduced with permission from . Copyright 2021, American Chemical Society. B. Design and application of lipid-unlocking CTB-reactive probe (L-CRP) for specific imaging of atherosclerotic plaques. The L-CRP activates in the presence of CTB and lipids, providing enhanced photoacoustic imaging signals and distinguishing atherosclerotic lesions from normal vessels. Reproduced with permission from . Copyright 2022, American Chemical Society. C. Fluorescence imaging reveals a fourfold greater accumulation of anti-CD47 NPs in the lipid core of human carotid plaques compared to free NPs, confirming their enhanced targeted binding efficacy. Reproduced with permission . Copyright 2020, John Wiley and Sons. D. Schematic for the plaque-targeted imaging with DCP liposomes and in vivo targeted imaging ability of plaque by PAI and FI. The successful recognition of aortic arch by photoacoustic imaging in which the green PA signal appeared in the left thoracic cavity was confirmed by ultrasonic imaging. Reproduced with permission . Copyright 2022, Elsevier.

Figure 4

Self-assembled nanoparticles for atherosclerosis drug delivery. A. Schematic illustrations of the macrophage hithking MP-QT-NPs for atherosclerosis treatment. Reproduced with permission from . Copyright 2022, Elsevier. B. Illustration of the therapeutic mechanism and Effects of p27-miRNA switch-p5RHH Nanoparticles. The p27-miRNA switch-p5RHH nanoparticles selectively inhibit restenosis and facilitate vessel healing. Reproduced with permission from . Copyright 2021, Elsevier. C. Illustration of the therapeutic mechanism and therapeutic effects of MSe1 nanozyme for atherosclerosis. Reproduced with permission from . Copyright 2023, John Wiley and Sons.

Figure 5

Self-assembled nanoparticles for atherosclerosis drug delivery. A. Structure of the self-assembled LMWH-IND prodrug nanoparticles for atherosclerosis treatment. Reproduced with permission . Copyright 2022, Elsevier. B. Illustrations of vitamin C encapsulating VC@cLAVs for treatment of atherosclerosis. VC@cLAVs enhanced the blood half-life of antioxidants and effectively reduced plaque area in vivo. Reproduced with permission . Copyright 2022, John Wiley and Sons. C. Illustration of DNA origami nanoparticle design and therapeutic mechanism for targeting M1 macrophages, reducing ROS, and mitigating foam cell formation in atherosclerotic plaques. Reproduced with permission from . Copyright 2024, American Chemical Society. D. Illustrations and therapeutic effects of carrier-free TAP nanomotors for atherosclerosis treatment. Reproduced with permission from . Copyright 2022, American Chemical Society.

Figure 6

ROS responsive nanoparticles for atherosclerosis drug delivery. A. Schematic illustration of ROS responsive nanoparticles loaded with lipid-specific AIEgen and anti-inflammatory drug for targeted diagnosis and treatment of atherosclerosis. Reproduced with permission . Copyright 2022, Elsevier. B. Schematic illustration for the ROS responsive lipid nanoparticles-loaded CAR-Ms for potential atherosclerosis therapy. Reproduced with permission . Copyright 2024, John Wiley and Sons.

Figure 7

Various stimuli responsive nanoparticles for atherosclerosis treatment. A. Schematic illustration of cathepsin K (CTSK)-responsive RAP@T/R NPs targeting atherosclerosis. Reproduced with permission . Copyright 2022, Ivyspring International Publisher. B. Illustration of ATP-responsive polyplexes for gene delivery in atherosclerosis treatment. Reproduced with permission . Copyright 2019, American Chemical Society. C. Dual-stimuli-responsive DMM nanoparticles for atherosclerosis theranostics. This platform co-delivers H₂S and O₂ gases within plaques, reducing hypoxia and inflammation while enabling MR imaging. The MnO₂ component reacts with ROS and acidic pH within plaques, triggering gas release and anti-inflammatory effects. Reproduced with permission . Copyright 2024, John Wiley and Sons.

Figure 8

Self-assembled nanoparticles for atherosclerosis vaccine development. A. Mice inoculated with L-IFPTA vaccine showed higher serum antibody titers, suggesting the effectiveness of L-IFPTA. Reprinted with permission . Copyright 2019, Elsevier. B. Mechanism of PCSK9-targeted BSANPs (Bovine Serum Albumin Nanoparticles) in enhancing LDL receptor recycling and reducing PCSK9-mediated degradation, thereby improving cholesterol metabolism and reducing atherosclerotic plaque formation. Reproduced with permission from . Copyright 2024, American Chemical Society. C. Construction and immunogenicity of PCSK9-NP, including its conjugation with GvO-Ferritin nanoparticle, immunization regimen in animal models. Reproduced with permission . Copyright 2024, Elsevier. D. Vaccination of the QβS100A9 vaccine implant in vivo successfully achieved higher and stable level of S100A9-specific IgG, and the percentage of atherosclerotic lesion in the QβS100A9 vaccine implant group was lower than that in the control group. Reproduced with permission . Copyright 2022, John Wiley and Sons.

Figure 9

Self-assembled nanoparticles for atherosclerosis theranostics. A. MRI and histological analysis showing the reduction of plaque size and inflammation in mice treated with HA-CC-RST nanoparticles compared to controls. Reproduced with permission . Copyright 2022, John Wiley and Sons. B. Schematic illustration of the synthesis of IR780-Gd-OPN nanomicelles and the use of mild phototherapy to inhibit the progression of atherosclerotic plaques by enhancing the expression of heat shock protein 27, which subsequently inhibits the NF-κB pathway. Reproduced with permission . Copyright 2024, Elsevier. C. Illustration of pH and ROS-responsive PA/ASePSD nanoplatform targeting atherosclerotic plaques and mitochondria, enabling targeted photoacoustic diagnosis and combination therapy for atherosclerosis. Reproduced with permission . Copyright 2023, John Wiley and Sons.

Figure 10

Self-assembled nanoparticles for atherosclerosis biosensing. A. Schematic illustration of synthesis of I₃^--RhB @PCN-224 and its application in detection and imaging of phosphorylation and glucose levels in early atherosclerosis model. Two-photon imaging of the thoracic aorta showed early atherosclerosis mice displayed elevated levels of protein phosphorylation and glucose concentrations. Reproduced with permission . Copyright 2023, John Wiley and Sons. B. Schematic illustration of synthesis of PCN-NP-HPZ and its application for monitoring pH and phosphate levels in atherosclerosis development. Two-photon imaging of the aorta showed the increased levels of pH and phosphorylation in atherosclerosis mice. Reproduced with permission . Copyright 2022, John Wiley and Sons.