Table 3 Some studies related to the application of engineered Exos in cardiovascular diseases

Direct (post-isolation)

Cardiac progenitor cell Exos were decorated with cardiac homing peptide using a DOPE-NHS linker

Rat model of infarction

Targeting efficiency↑, Fibrosis↓, Infarct and scar size↓, Cell proliferation↑, angiogenesis↑

[125]

The surface of Exos was decorated with cardiac targeting peptide and loaded with

NOX4 siRNA

Mouse model of

angiotensin II-induced atrial fibrillation

Targeting efficiency↑,

Cardiac function↑, Fibrosis↓, Arrhythmia inducibility↓

[188]

The surface of Exos was decorated with cardiac targeting peptide using DBCO Sulfo-NHS and miR-34a were elevated inside Exos using CRISPR-Cas9-

Mouse model of myocardial infarction

Targeting efficiency↑,

hydrogen peroxide-induced apoptosis↓,

[101]

The surface of MSC Exos was decorated with fluorinated peptide dendrimers by incubation

In vitro incubation with HUVECs

HUVEC uptake↑, angiogenesis↑, migration↑

[129]

Mycophenolic acid was loaded into RAW 264.7 macrophage Exos using passive incubation and in TritonX-100

In vitro rat cardiomyoblasts,

Uptake in rat cardiomyoblasts↑, Inflammation↓, Intracellular oxidative stress↓

[124]

Using Sonication melatonin was loaded into MSC Exos

Hypoxia/serum-deprived rat cardiomyoblasts, and

and mouse model of infarction

Uptake levels↑, Apoptosis↓, Oxidative stress↓, Fibrosis↓, and

microvessel formation (CD31) ↑

[189]

Using electroporation,

miR-126 was loaded onto the cardiac progenitor cell Exos

rat model of ischemia–reperfusion, and in vitro cardiac endothelial cells

Uptake levels↑, Angiogenesis↑, Fibrosis↓, Myocardial function↑, Hypertrophy↓, Microvascular density (isolectin B4⁺, α-SMA⁺ cells↑)

[120]

The surface of MSC Exos was cloaked with platelet membrane using extrusion

In vitro incubation with human coronary artery ECs, and mouse model of myocardial infarction

Uptake levels↑, Tubulogenesis↑, Proliferation↑, Mitochondrial activity↑, Inflammation↑, Targeting efficiency↑, infarct size and fibrosis↓,

[190]

In-direct (pre-isolation)

Cardiosphere-derived Exos were coated with Lamp2b- and cardiomyocyte-specific peptide using expressing plasmids in parent cells

In vitro incubation with cardiomyocytes, HUVECs, and cardiac fibroblasts, and mice

Uptake by cardiomyocytes↑, Retention time↑, Apoptosis↓, Hypertrophy↓

[114]

HEK 293 cell Exos were decorated with

cardiac-targeting peptide-Lamp2b using expressing plasmid

H9C2 cells, and mice

Delivery efficiency↑,

[115]