Understanding the Protective Role of Exosomes in Doxorubicin-Induced Cardiotoxicity

Table 2

Summary of studies using EXOs/EVs for the treatment of DIC.

Parent cell	EVs type	Cargo	Cargo formulation	Study model	Antitumor parameters	Cardiotoxicity parameters	Ref
CSCs	EXOs	—	EXOs	In vivo (mice); in vitro (NRCMs)	NA	EF↑, FS↑, apoptosis↓, fibrosis↓, immune response↓	[115]
MSCs	EXOs	DOX	EXOs-DOX	In vivo (MG63 cells, H9C2 cells)	MG63 cells: cell uptake rate↑, cell viability↓	H9C2 cells: cell viability↑	[122]
MDA-MB-231, STOSE, MDAMB-231 CD63-GFP and STOSE CD63-GFP cell lines	EXOs	DOX	EXOs-DOX	In vivo (mice); in vitro (human myocardial endothelia cells)	Maximum tolerated dose of DOX↑, tumor volume↓	The ability to cross a reconstructed myocardial endothelial monolayer↓, vacuoles↓, and myofibril disorganization↓ in H&E staining	[124]
MDA-MB-231 and HCT-116 cell lines	EXOs	DOX	EXOs-DOX	In vivo (mice); in vitro (MDA-MB-231 cells)	Cell viability↓, tumor volume↓	Distribution of DOX in the heart↓, no cardiac damage in H&E staining	[123]
HEK-293 cells	EXOs	miR-21a	EXOs^siClathrin, followed by EXOs^miR-21a	In vivo (mice)	NA	miR-21a-5p expression in heart↑, EF↑, FS↑	[120]
HEK-293 cells	EVs	Cx43, DOX	EVs^Cx43+-DOX	In vivo (mice); in vitro (4T1^luc2 cells)	Cell viability↓, cell proliferation↓, cell motility↓, colony formation↓, tumor growth↓, apoptosis↑	Fibrosis↓, histopathological changes↓, COX-2↓, HSP25↓	[121]
NA	EXOs	miR-21	UTMD+EXOs^miR-21	In vivo (mice)	NA	miR-21 delivery efficiency↑, EF↑, E/A value↑	[126]
LIM1215 cells	EXOs	DOX	A33Ab-US- EXOs-DOX	In vivo (mice); in vitro (LIM1215 cells)	Cell uptake rate↑, cell viability↓, half-maximal inhibitory concentrations↓, necrosis↑, apoptosis↑, tumor volume↓	Apoptosis↓, cardiac damage↓	[127]
Mouse immature dendritic cells	EXOs	DOX	iRGD-EXOs-DOX	In vitro (MDA-MB-231 cells); in vivo (mice)	DOX delivery efficiency↑, cell viability↓, tumor volume↓	CK-MB↓, AST↓, no cardiac damage in H&E staining	[129]

CSCs: cardiac stem cells; EXOs: exosomes; NRCMs: neonatal rat cardiomyocytes; MSCs: mesenchymal stem cells; Cx43: the gap junction protein connexin43; UTMD: ultrasound-targeted microbubble destruction; FS: shortening fraction; EF: ejection fraction; COX-2: cyclooxygenas-2; HSP25: heat shock protein 25; CK-MB: creatine kinase-MB; AST: aspartate transaminase; A33Ab-US-EXOs-DOX: DOX loaded in exosomes coated surface-carboxyl superparamagnetic iron oxide nanoparticles with A33 antibodies.