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Table 2 Application of exosomes in tumor therapy

From: Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application

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]

  1. 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