Recent strategies to design vascular theranostic nanoparticles

Abstract

Vascular disease is a leading cause of death and disability worldwide. Current surgical intervention and treatment options for vascular diseases have exhibited limited long-term success, emphasizing the need to develop advanced treatment paradigms for early detection and more effective treatment of dysfunctional cells in a specific blood vessel lesion. Advances in targeted nanoparticles mediating cargo delivery enables more robust prevention, screening, diagnosis, and treatment of vascular disorders. In particular, nanotheranostics integrates diagnostic imaging and therapeutic function into a single agent, and is an emerging platform towards more effective and localized vascular treatment. This review article highlights recent advances and current challenges associated with the utilization of targeted nanoparticles for real-time diagnosis and treatment of vascular diseases. Given recent developments, nanotheranostics offers great potential to serve as an effective platform for targeted, localized, and personalized vascular treatment.

Keywords: nanotheranostics; vascular diseases.

Figure 1

Schematic illustration of theranostic nanoparticles (e.g., micelles, liposomes, nanospheres, dendrimers, quantum dots, iron oxide particles, etc.) embedded with therapeutic and imaging agents.

Figure 2

Macrophage-targeted theranostic nanoparticle (TNP) for photodynamic therapy of atherosclerosis disease. A) Aqueous solution of TNPs were stable for months without precipitation (pH 7.4) (left), and visualized through MRI (middle) and fluorescence imaging (0.01 mg Fe per mL) (right). B) Cellular uptake and light-induced phototoxicity of the TNPs (i) Flow cytometic analysis of time-dependent accumulation of TNPs as confirmed by cell-associated fluorescence (0.1 mg Fe per mL). (ii) Fluorescence microscopy image shows an uptake and intracellular localization of the TNPs after 3h incubation with RAW 264.7 cells (0.1 mg Fe per mL). (iii) Cell viability of human macrophages after incubation (1 h) with the respective nanoparticles (0.2 mg Fe per mL) and light treatment (42 mW cm^-2, 7.5 J), as determined by a MTS assay. The TNP Dark experiment consisted of cells incubated with TNP that did not receive PDT treatment. Control cells were incubated with PBS. All results are relative to the control cells (100 %). (iv) Dose-dependent phototoxicity of TNP in RAW 264.7 cells after incubation (1 h) and light treatment (42 mW cm-2, 7.5 J), as determined by the MTS assay. Reproduced with permission from.

Figure 3

Gold nanorods (Au NRs) as a theranostic platform for imaging and photothermal therapy (PTT) of inflamed macrophages in a mouse model of femoral artery restenosis. (A, B) In vivo 3D micro-CT images of the femoral artery before (down; B) and after (up; A) intravenous injection of Au NRs. C, D) IR thermal images of Apo E mice injected with the Au NRs (the right mouse, indicated region 11) or saline (the left mouse, indicated region 12) via intravenous injection, respectively, irradiated with an 808 nm laser (2 W/cm²) at a time point of 0 (up; C) and 300 s (down; C). E) The temperature profiles in regions 11 and 12 as a function of irradiation time. F, G) The representative histological examination sections stained with CD68, of the corresponding ex vivo femoral artery restenosis regions, after irradiation for 10 min. Irradiation was done by an 808 nm laser with the safe power density of 2 W/cm². H) Statistical analysis of the macrophage number between Au NRs with and without PTT. Scale bars indicate 100 μm. Reproduced with permission from .

Figure 4

PREY(GSPREYTSYMPH)-targeted liposome for selectively targeting atheroprone vasculature. A) Ahterosclerosis preferentially develops in the regions of disturbed blood flow. PREY peptide (GSPREYTSYMPH) of nanocarrier was selectively accumulated in the luminal surface of endothelial cells caused by the atheroprone flow. B) Vascular targeting of PREY-nanocarriers. (i) En face preparations of ligated left carotid arteries with scrambled and targeted liposome injections (Red = liposome fluorescence, blue = nuclei). (ii) Cross section of a mouse aortic arch showing targeted liposome accumulation in the lesser curvature of the aortic arch (inset) (green = elastin autofluorescence, red = liposome fluorescence; Scale bar = 250 μm, inset scale bar = 100 μm). C) Liposome delivery of tetrahydrobiopterin (BH₄) significantly reduced plaque burden in the ligated left carotid artery of ApoE^-/- mice fed a high fat diet for 7 days. Plaque is outlined in red, and lumen is outlined in blue. Scale bars = 100 μm. Reproduced with permission from .