Table 2.

Application of exosomes in tumor therapy

Application		Source	Cargo	Disease	Method of administration	Biodistribution and pharmacokinetics	Outcome/in vitro	Outcome/in vivo	Refs.
Drug delivery vectors	Small molecules	4T1 cell	DOX	Breast cancer	Intravenous injection	It was absorbed by the liver and spleen within 20 min of injection, and in addition to significant uptake in the liver and spleen, uptake was observed in the lungs and kidneys after 24 h	–	Significantly inhibited tumor growth	[107]
		MGC803 cell	DOX	Gastric cancer	Intravenous injection	The signal in the tumor area gradually increased within 48 h, whereas it decreased in the liver	Enhanced tumor cell killing effect	Significant tumor growth inhibition	[141]
		Bel7402 cell	DOX	Liver cancer	Intravenous injection	Increased tumor site accumulation and less normal organ accumulation were observed 24 h after injection compared with free drug	Exhibited the strongest cytotoxicity against tumor cells	Significant anticancer activity and prolonged survival time	[142]
		bone marrow MSCs	DOX	osteosarcoma	Intravenous injection	1 h after administration, exosome fluorescence was mainly observed in the liver region. At 12 h after administration, the fluorescence intensity of exosomes in the tumor area was strong	Significant cell uptake efficiency and antitumor effect	Tumor growth was significantly inhibited and cardiac toxicity was significantly reduced	[145, 146]
		RAW 264.7	paclitaxel	Lewis Lung Carcinoma	Intravenous injection	Exosomes were shown to colocalize with lung metastases 4 h after administration	Tumor cytotoxicity was more than doubled	Efficiently targeted lung metastases and significantly inhibited tumor growth	[144]
		Raw264.7	TRAIL + triptolide	Malignant melanoma	Intravenous injection	Its accumulation in the tumor site reached its peak at 6 h after injection and remained at the tumor site after 24 h	Inhibited proliferation, invasion, and migration and promoted apoptosis	Significantly inhibited tumor progression and reduced the toxicity of triptolide	[151]
	Biomacromolecules	YUSAC 2	Survivin-T34A + gemcitabine	pancreatic cancer	–	–	It significantly increased the apoptosis of tumor cells in a time-dependent manner	–	[158]
		HEK293T epithelial cells	CRISPR/Cas9 plasmid DNA	胰腺癌	Intravenous/intratumoral injection	–	Targeting mutant Kras G12D in pancreatic cancer cells and inducing target gene deletion	Inhibition of tumor growth in homologous subcutaneous and orthotopic models of pancreatic cancer	[164]
		Lewis lung carcinoma cell	miR-29a-3p	Lewis Lung Carcinoma	Intravenous injection	–	Tumor cell adhesion, colony formation, invasion, and proliferation were decreased	Targeted lung metastases and downregulated lung collagen	[167]
		HEK293T epithelial cells	iRGD modification Carnitine palmitoyltransferase 1A siRNA	Oxaliplatin resistant colon cancer	Intravenous injection	Targeting of the tumor approximately 6 h after injection	Inhibition of tumor cell proliferation and reversal of oxaliplatin resistance	Reversal of oxaliplatin resistance and inhibition of tumor growth	[171]
Immunotherapy		CAR-T cell	CAR	Human tumor cell lines expressing EGFR/HER2	Intravenous injection	-	Significant tumor cytotoxicity	Dose-dependent tumor growth inhibition	[185]
		human umbilical vein endothelial cell	Anti-PD-L1 + Anti-CD40 + cGAMP	Melanoma	Intravenous injection	At 2 h after injection, the tumor site showed obvious accumulation of exosomes, which continued to accumulate at the tumor site after 24 h	Tumor targeting and immune activation capabilities	Significantly delayed tumor growth and improved the survival rate of mice	[188]
Penetration of biological barrier		bEND.3 cell	DOX or paclitaxel	Brain cancer	Main vein injection	At 18 h after injection, exosomes were delivered across the BBB to the brain	Increased cytotoxicity in cancer cells	Xenograft tumor growth was significantly reduced	[192]
		bEND.3 cell	VEGF siRNA	Brain cancer	Main vein injection	Increased the distribution of siRNA in the brain by more than four times	Significant inhibition of VEGF	Xenograft tumors exhibited little fluorescence in the brain	[193]
		THP-1 induced M1 macrophages	Angiopep-2 + STAT3 siRNA	Glioblastoma	Intravenous injection	A strong accumulation of exosomes was observed in the brain 24 h after injection	Significant apoptosis of GBM cells	Significantly inhibited tumor growth and improved the median survival time of tumor-bearing mice	[194]
Improving the tumor microenvironment		HEK293T epithelial cells	STAT6-ASO	Colorectal cancer and hepatocellular carcinoma	Intravenous/intratumoral injection	95% of the intravenous dose was administered in the liver; After intratumoral administration, the highest mean fluorescence intensity was shown at TAM	Immunosuppressive M2 macrophages were reprogrammed into proinflammatory M1 macrophages	Potent antitumor activity and M1 macrophage reprogramming, as well as TME remodeling and CD8 + T-cell-dependent adaptive antitumor immune responses	[198]
		4T1 cancer cells	MnCO	metastatic breast cancer	Intravenous injection	High accumulation at the tumor site	Efficient killing and targeting ability of tumor cells	Significantly inhibited tumor growth and enhanced tumor radiosensitivity	[199]
		4T1 cancer cells	DOX-loaded long-circulating and pH-sensitive liposomes	breast cancer	Intravenous injection	–	Significantly reduced tumor cell viability	Stronger tumor killing effect and less acute toxicity as well as tissue/organ damage such as heart and spleen; reduction in the number of lung metastases	[201, 202]

DOX: doxorubicin; STAT: signal transducers and activators of transcription; ASO: antisense oligonucleotide; VEGF: vascular endothelial growth factor; MSCs: mesenchymal stem cells; TRAIL: tumor necrosis factor-related apoptosis-inducing ligand; T34A: Thr34 → Ala; siRNA: small-interfering RNA; CAR T-cells: genetically engineered T-cells expressing a chimeric antigen receptor; EGFR: epidermal growth factor receptor; HER2: human epidermal growth factor receptor-2; TAM: tumor-associated macrophages