Nature-inspired nanocarriers for improving drug therapy of atherosclerosis

Abstract

Atherosclerosis (AS) has emerged as one of the prevalent arterial vascular diseases characterized by plaque and inflammation, primarily causing disability and mortality globally. Drug therapy remains the main treatment for AS. However, a series of obstacles hinder effective drug delivery. Nature, from natural micro-/nano-structural biological particles like natural cells and extracellular vesicles to the distinctions between the normal and pathological microenvironment, offers compelling solutions for efficient drug delivery. Nature-inspired nanocarriers of synthetic stimulus-responsive materials and natural components, such as lipids, proteins and membrane structures, have emerged as promising candidates for fulfilling drug delivery needs. These nanocarriers offer several advantages, including prolonged blood circulation, targeted plaque delivery, targeted specific cells delivery and controlled drug release at the action site. In this review, we discuss the nature-inspired nanocarriers which leverage the natural properties of cells or the microenvironment to improve atherosclerotic drug therapy. Finally, we provide an overview of the challenges and opportunities of applying these innovative nature-inspired nanocarriers.

Keywords: atherosclerosis; drug delivery; membrane-coating; nature-inspired nanocarriers; stimuli-responsive.

Graphical abstract

Figure 1.

The delivery challenges in nanomedicines for as treatment.

Figure 2.

A schematic overview of nature-inspired nanocarriers for drug delivery to treat as.

Figure 3.

RBCm-coated nanoparticles RBC/RAP@PLGA for treatment of as. (A) Schematic illustration of RBC/RAP@PLGA for as treatment. (B) Transmission electron microscope images of nanoparticles. Scale bar: 100 nm. (C) Pharmacokinetic studies of RBC/DiD@PLGA and DiD@PLGA. (D) The ex vivo fluorescence images of the aorta and (E) quantitative data of fluorescence signals accumulated in the aorta of ApoE⁻/⁻ mice treated with different formulations (n = 3). Adapted with permission from Ref. [75].

Figure 4.

Platelet-mimetic nanocarriers for targeted therapy of AS. (A) Schematic illustration of P-Lipo preparation and its targeting treatment for AS. (B) White light images and fluorescence images (flu) of the aorta after injection of different formulations. Scale bar: 5 mm. (C) Biodistribution in major organs of mice 2 h after intravenous injection. (D) Representative images of total aortas from each group. Quantitative analysis of (E) aortic lesion and (F) plaque area. Adapted with permission from Ref. [78].

Figure 5.

Biomimetic membrane-coated HA-M@PB@ (PC + ART) NPs for treatment of AS. (A) Schematic illustration of HA-M@PB@ (PC + ART) NPs and their treatment for AS. (B) In vivo pharmacokinetic curves after intravenous injection of PB and HA-M@PB. (C) The fluorescence images of the aorta after intravenous injection of different formulations. Adapted with permission from Ref. [81].

Figure 6.

Macrophage-mediated hitchhiking delivery for treatment of AS. (A) Schematic illustration of hitchhiking delivery. (B) The fluorescence images of the aorta after intravenous injection and (C) quantitative analysis by using in vivo imaging system. (D) The microscope images of aortic lesions and (E) quantitative data of lesions on the intimal surface of the aorta. Adapted with permission from Ref. [82].

Figure 7.

Targeted delivery of P-EVs for treatment of AS. (A) Preparation diagram of P-EV by fusing platelet membrane and MSC-EV and (B) treatment diagram of P-EV for treatment of AS. (C) Fluorescence images of the aortas after intravenous injection. (D) Images of the aortas after the treatment with different formulations and (E) quantitative data of plaque area in the aortas. Adapted with permission from Ref. [84].

Figure 8.

The dextran-based ROS-responsive nanoparticle, LFP/PCDPD, for targeted delivery and controlled release of drugs. (A) Preparation diagram and (B) treatment diagram of ROS triggered LFP/PCDPD. (C) Accumulative drug release of LFP/PCDPD under different solutions. (D) Photographs of the aortas treated with different formulations. Adapted with permission from Ref. [115].

Figure 9.

ROS-Responsive size-reducible HA-Fc/${\text{NP}}_{\text{ST}}^3$ nanoassemblies for targeted treatment of AS. (A) Preparation diagram and (B) treatment diagram of ROS-responsive HA-Fc/${\text{NP}}_{\text{ST}}^3$ nanoassemblies. (C) Penetration of different formulations in spheroids and (D) quantification of fluorescence intensity in the center of spheroids. Adapted with permission from Ref. [116].

Figure 10.

The carrier-free nanomotor TAP for targeting macrophages in vulnerable plaque. (A) The synthetic process of nanomotor TAP. (B) Treatment process diagram of TAP for targeting macrophages in vulnerable plaque. (C) The trajectory and the distribution of speed of TAP nanomotors. (D) Cellular uptake images of HUVECs and raw 264.7 treated with different formulations. Adapted with permission from Ref. [118].

Figure 11.

The CSNP for treatment of AS. (A) Schematic of CSNP preparation and cargo-switching. (B) Competitive binding of cholesterol (CHOL) and statin (ST) to CD. (C) Representative histological images of the left carotid artery (LCA) sections and (D) quantification of plaque area. (E) Quantification of macrophage area in the LCA sections. Adapted with permission from Ref. [119].