Table 4.

EV-based therapeutic modalities.

Modality	Cargoes	Anti-Tumor Effect
EV as a drug delivery system	MiR-195 [70,108]	Suppression of CCA cells in vitro Downregulation of CDK6, CDK1, CDK4, VEGF Transfected LX2 (hepatic stellate cell line) Suppression of tumor growth Elongation of survival of the animal CCA model (rat) via limiting the desmoplastic reaction of stromal cells ↓ a-SMA and Ki67 expression levels in the rats
	MiR-30e [69,109]	Transfected HuCCT1 cells with miR-30e Suppression of CCA growth and progression miR-30e that targets Snail (EMT-inducible transcription factor) EMT suppression and inhibition via Snail inhibition manner
	F-FU [110]	MSC-derived exosomes artificially loaded with 5-FU in vitro EVs-5FU proved to be more effective in CCA cell elimination Vs free-5FU
Vaccination SIRT-targeting EVs [112] EV as therapeutic target BMI1 knockdown Μyriocin TFEB agonist curcumin analog C1 [113]	Tetraspanins O. viverrini Evs [111]	The mechanism of the response to O. viverrini challenge is via the tetraspanin O. viverrini antibodies block the uptake and internalization of O. viverrini EVs by host cholangiocytes Decrease of the O. viverrini burden, ↓ worm growth (shorter)
	BMI1 [79] Ceramide [80]	Selected for patients with inoperable tumors Radioactive materials are delivered via an arterial catheter, directly into the tumor vasculature SIRT for the modification of EV immune profiling ↓ PLT-derived EVs (CD41b, CD62P and CD42a) post-treatment ↓ CD44 and CD24—EVs after the SIRT ↓ tumor growth and progression. ↓ EV derived by tumor progenitors and stem cells CD133 after SIRT CCA tumor progression/growth Enhancing the ICI effect Suppression of ceramide production Ceramide-induced inflammation Suppression of vascular invasion Aiming at the biogenetic pathway of exosomes Prevention of CCA metastatic dissemination and cancer relapse

↓ downregulated.