Table 4.

Preclinical trials of sEV-encapsulated ncRNAs as therapeutics in PDAC

Ref	sEV donor	Cargo loading	ncRNA	Mouse model	Therapeutic intervention	Result
Kamerkar et al. [193]	Human foreskin fibroblast	Electroporation	siKRASG12D	orthotopic PANC-1/BxPC-3/KPC689 xenografts	Intraperitoneal injection of sEVs	Prolonged survival, inhibition of metastasis
				KPC/KTC GEMM
Mendt et al. [206]	BM-MSC	Electroporation	siKRASG12D	Orthotopic KPC689/PANC-1 xenograft	Intraperitoneal injection of sEVs	Prolonged survival, enhanced effect of gemcitabine
				Orthotopic PATX-60 PDX
				PKS GEMM
Ding et al. [201]	HUC-MSC	Transfection	miR-145-5p mimic	Subcutaneous PANC-1 xenograft	Intratumoral injection of sEVs	Reduced tumor growth
Wu et al. [202]	BM-MSC	Transfection	miR-126-3p mimic	Subcutaneous xenograft	Co-injection of BM-MSCs	Reduced tumor growth
Shang et al. [204]	BM-MSC	Transfection	miR-1231 mimic	Subcutaneous BxPC-3 xenograft	Tail vein injection of sEVs	Reduced tumor growth
Zuo et al. [207]	HEK293	Ultrasound	miR-34a mimic	Subcutaneous Panc28 xenograft	Intravenous injection of sEVs	Reduced tumor growth
Xu et al. [208]	PANC-1	Electroporation	siPAK4	Subcutaneous PANC-1 xenograft	Intratumoral injection of sEVs	Reduced tumor growth
Zhou et al. [209]	BM-MSC	Electroporation	siGalectin9	Orthotopic PANC-02 xenograft	Tail vein injection of sEVs	Enhanced effect of immunotherapy

5-FU, fluorouracil; BM, bone marrow; GEMM, genetically engineered mouse model; HUC, human umbilical cord; MSC, mesenchymal stem cell; PDX, patient-derived xenograft; Ref., reference