Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery

Abstract

Thrombotic disease has been listed as the third most fatal vascular disease in the world. After decades of development, clinical thrombolytic drugs still cannot avoid the occurrence of adverse reactions such as bleeding. A number of studies have shown that the application of various nano-functional materials in thrombus-targeted drug delivery, combined with external stimuli, such as magnetic, near-infrared light, ultrasound, etc., enrich the drugs in the thrombus site and use the properties of nano-functional materials for collaborative thrombolysis, which can effectively reduce adverse reactions such as bleeding and improve thrombolysis efficiency. In this paper, the research progress of organic nanomaterials, inorganic nanomaterials, and biomimetic nanomaterials for drug delivery is briefly reviewed.

Keywords: biomimetic nanomaterials; drug delivery system; inorganic nanomaterials; organic nanomaterials; thrombolytic drugs; thrombosis.

Figure 1

Schematic diagram of thromboembolic disease. Created with BioRender.com (accessed on 3 March 2024).

Figure 2

Schematic of a nanocarrier for delivery of thrombolytic drugs for thrombolysis. Created with BioRender.com (accessed on 3 March 2024).

Figure 3

(A) After the injection of four different reagents into the thrombus model, the infarct area demonstrated that MNP-rtPA has a significant thrombolytic effect. (B) Representative images of 2,3,4 triphenyltetrazolium chloride (TTC) staining. Reproduced with permission [36]. Copyright 2019, Elsevier.

Figure 4

Schematic of the synthesis of asymmetric-structured bowl-shaped mesoporous silica nanoparticles and their thrombolytic process. Reproduced with permission [60]. Copyright 2021, Elsevier.

Figure 5

(A) Experimental setup for plasmin-loaded CTNP evaluation in the zebrafish venous thrombosis model, with representative brightfield images showing clot formation after laser injury; (B) time-to-occlusion (TTO) study showed that CTNPs loaded with plasmin could significantly prevent the formation of blood clots; (C) time-to-recanalization (TTR) study showed that CTNPs encapsulated with plasmin could achieve effective vascular recanalization within 20 min. Reproduced with permission, **** p ≤ 0.0001; ns not significant. [75]. Copyright 2022, Elsevier.

Figure 6

Average fluorescence intensity of thrombus after intravenous injection of cRGD-ICG-uPA NPs (20 U/g) on mouse mesenteric vascular thrombosis models, and in vivo fluorescence images at representative time points (n = 3). Reproduced with permission [96]. Copyright 2022, Frontiers.

Figure 7

Schematic of a hydrogel drug delivery system capable of releasing drugs in response to mechanical stress at atherosclerotic plaques. The letters “a–d” in the figure caption denote different structures formed by the nanocarrier at various locations within the vascular system. Reproduced with permission [114]. Copyright 2019, Elsevier.

Figure 8

(A) Pharmacokinetics study of nanoparticles in blood circulation on rat; (B) the mean fluorescence intensity of the binding ability of nanoparticles to blood clot ex vivo; (C) D-dimer ELISA kit was used to detect the content of D-dimer in serum with PBS, RFNP, and PFNP injection, * p ≤ 0.05. Reproduced with permission [126]. Copyright 2020, ACS Publications.