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. 2024 Apr 6;32(2):200800. doi: 10.1016/j.omton.2024.200800

Table 3.

Summary of exosome-based therapeutic agents, animal studies, and treatment parameters

First author Year Exosome-based therapeutic agent Methods for generating and loading Treated groups Quantity Volume of injection Route of administration Frequency of administration Euthanasia
Wang et al.31 2018 EXO-DEPT cell engineering and incubation 1. untreated (PBS or saline) NR 100 μL i.p. days 1, 2, 4, 6, 8, 9, 11, 14 NR
2. EVs only 2 × 109 EV 100 μL i.p. days 1, 8 NR
3. CNOB (6-chloro-9-nitro-5-oxo-5H-benzo(a)phenoxazine) only 3 mg/kg 100 μL i.p. days 2, 4, 6, 9, 11, 14 NR
4. undirected loaded EVs + CNOB (3 mg/kg) 2 × 109 EV 100 μL i.p. + i.v. days 1, 2, 4, 6, 8, 9, 11, 14 NR
5. Exo-DEPTs + CNOB (3 mg/kg) 2 × 109 EV 100 μL i.p. + i.v. days 1, 2, 4, 6, 8, 9, 11, 14 NR
Zhou et al.32 2021 EVs-424 cell transfection with miR-424 mimics 1. untreated (PBS) NR 100 μL i.t. days 0, 3, 6, 9, 12 45 days
2. EV-unloaded miR-424 30 μg 100 μL i.t. days 0, 3, 6, 9, 12 45 days
3. EV-424 30 μg 100 μL i.t. days 0, 3, 6, 9, 12 45 days
Zhao et al.33 2020 CBSA/siS100A4@Exosome incubation 1. untreated (saline) NR NR i.v. days 14, 16, 18, 20 30 days
2. free siS100A4 1 mg/kg siRNA NR i.v. days 14, 16, 18 ,20 30 days
3. CBSA/siS100A4 (1 mg/kg siRNA) NR NR i.v. days 14, 16, 18, 20 30 days
4. CBSA/siS100A4@Liposome (1 mg/kg siRNA) NR NR i.v. days 14, 16, 18, 20 30 days
5. CBSA/siS100A4@Exosome (1 mg/kg siRNA) NR NR i.v. days 14, 16, 18, 20 30 days
6. CBSA/siNC@Exosome (1 mg/kg siRNA) NR NR i.v. days 14, 16, 18, 20 30 days
Xie et al.34 2021 Exo-DOX sonication 1. untreated (saline) NR NR i.v. every 3 days (8 doses) 7 weeks
2. exosome 150 μg/kg NR i.v. every 3 days (8 doses) 7 weeks
3. free DOX 300 μg/kg NR i.v. every 3 days (8 doses) 7 weeks
4. Exo-DOX(300 μg/kg DOX) NR NR i.v. every 3 days (8 doses) 7 weeks
Wang et al.35 2019 PTX- M1-Exos sonication 1. untreated (PBS) NR NR i.v. every 3 days 27 days
2. PTX 5 mg/kg NR i.v. every 3 days 27 days
3. M1-Exos NR NR i.v. every 3 days 27 days
4. PTX-M1-Exos (5 mg/kg PTX) NR NR i.v. every 3 days 27 days
Tian et al.36 2020 ID@E-MSNs incubation for ID@MSNs and sonication for ID@E-MSNs 1. untreated (PBS) NR NR i.v. days 0, 3 16 days
2. free ICG 2 mg/kg NR i.v. days 0, 3 16 days
3 free DOX 0.5 mg/kg NR i.v. days 0, 3 16 days
4. ID@MSNs (2 mg/kg ICG + 0.5 mg/kg DOX) NR NR i.v. days 0, 3 16 days
5. ID@E-MSNs (2 mg/kg ICG + 0.5 mg/kg DOX) NR NR i.v. days 0, 3 16 days
Si et al.37 2022 mAb-EV-Ver-A synthesis for Ab attachment via linker and incubation for Ver-A primary TNBC xenograft 1. untreated (PBS) NR NR i.v. every 3 days (4 doses) 20 days
2. EGFR/CD47 mAb-EV NR NR i.v. every 3 days (4 doses) 20 days
3. EGFR/CD47 mAb-EV-Ver-A (0.5 mg/kg Ver-A) NR NR i.v. every 3 days (4 doses) 20 days
4. EGFR/CD47 mAb-EV-Ver-A (1.5 mg/kg Ver-A) NR NR i.v. every 3 days (4 doses) 20 days
5. EGFR/CD47 mAb-EV-Ver-A (2 mg/kg Ver-A) NR NR i.v. every 3 days (4 doses) 20 days
6. EGFR/CD47 mAb-EV-Ver-A (2.5 mg/kg Ver-A) NR NR i.v. every 3 days (4 doses) 20 days
7. EGFR mAb-EV-Ver-A (0.5 mg/kg Ver-A) NR NR i.v. every 3 days (4 doses) 20 days
8. CD47mAb-EV-Ver-A (0.5 mg/kg Ver-A) NR NR i.v. every 3 days (4 doses) 20 days
PDX 1. untreated (PBS) NR NR i.v. days 0, 4, 9, 15, 21, 26 NR
2. EV NR NR i.v. days 0, 4, 9, 15, 21, 26 NR
3. mAb-EV-Ver-A (0.5 mg/kg Ver-A) NR NR i.v. days 0, 4, 9, 15, 21, 26 NR
Pi et al.38 2018 EGFRaptamer/EV/siSurvivin transfection for siRNA and incubation for aptamer display 1. untreated (PBS) NR NR i.v. once a week 9 weeks
2. EGFRaptamer/EV/siScramble 0.5 mg siRNA/5 mg EV/kg mice NR i.v. once a week 9 weeks
3. EGFRaptamer/EV/siSurvivin 0.5 mg siRNA/5 mg EV/kg mice NR i.v. once a week 9 weeks
Peng et al.39 2022 immRNA and 3p-125b-ASO-loaded RBCEV with EGFR nanobody transfection for RNA conjugation with tetrameric streptavidin and biotinylated anti-EGFR nanobody intratumorally NSG-SGM3 models 1. untreated NR NR i.t. days 3, 6, 9,1 2, 15 18 days
2. NC RNA-EVs 2.5 mg/kg NR i.t. days 3, 6, 9, 12, 15 18 days
3. immRNA-EVs 2.5 mg/kg NR i.t. days 3, 6, 9, 12, 15 18 days
intratumorally BALB/c models 1. untreated NR NR i.t. days 3, 6, 9, 12, 15 18 days
2 .NC RNA-EVs 5 mg/kg NR i.t. days 3, 6, 9, 12, 15 18 days
3. immRNA-EVs 2.5 mg/kg NR i.t. days 3, 6, 9, 12, 15 18 days
4. 3p-125b-ASO-EVs 5 mg/kg NR i.t. days 3, 6, 9, 12, 15 18 days
intrapulmonary models 1. untreated NR NR i.v. days 2, 4, 6, 8, 10 11 days
2. NC RNA-EVs 25 mg/kg NR i.v. days 2, 4, 6, 8, 10 11 days
3. immRNA-EVs 25 mg/kg NR i.v. days 2, 4, 6, 8, 10 11 days
4. Ctrl-VHH-immRNA-EVs 25 mg/kg NR i.v. days 2, 4, 6, 8, 10 11 days
5. EGFR-VHH-. immRNA-EVs 25 mg/kg NR i.v. days 2, 4, 6, 8, 10 11 days
O’Brien et al.40 2018 EV-miR379 enriched cell engineering 1. MSC-379 1 × 106 cell NR i.v. once a week 6 weeks
2. 1 × 106 MSC-NTC 1 × 106 cell NR i.v. once a week 6 weeks
3. 2.6 × 107 MSC-NTC EVs 2.6 × 107 particles NR i.v. once a week 6 weeks
4. MSC-379 EVs 2.6 × 107 particles NR i.v. once a week 6 weeks
Naseri et al.41 2018 MSCs-Exo-loaded LNA-anti-miR-142-3p sonication 4T1 tumor 1. untreated (PBS) NR NR i.v. every 48 h 36 days
2. unloaded MSCs-Exo 30 μg NR i.v. every 48 h 36 days
3. MSCs-Exo loaded with LNA-anti-miR negative control 30 μg NR i.v. every 48 h 36 days
4. MSCs-Exo loaded with LNA-anti-miR-142-3p 30 μg NR i.v. every 48 h 36 days
TUBO tumor 1. untreated (PBS) NR NR i.v. every 48 h 40 days
2. unloaded MSCs-Exo 30 μg NR i.v. every 48 h 40 days
3. MSCs-Exo loaded with LNA-anti-miR negative control 30 μg NR i.v. every 48 h 40 days
4. MSCs-Exo loaded with LNA-anti-miR-142-3p 30 μg NR i.v. every 48 h 40 days
Martins-Marques et al.42 2016 EV (Cx43+) DOX electroporation 1. untreated (PBS) NR NR i.t. days 5, 8, 11 day 11
2. EV CX43− NR NR i.t. days 5, 8, 11 day 11
3. EV CX43+ NR NR i.t. days 5, 8, 11 day 11
4. DOX 2 mg/kg NR i.t. days 5, 8, 11 day 11
5. EV (CX43−) DOX (2 mg/kg) NR NR i.t. days 5, 8, 11 day 11
6. EV (CX43+) DOX (2 mg/kg) NR NR i.t. days 5, 8, 11 day 11
Li et al.43 2020 MEP-D incubation for DOX loading in PLGA
co extrusion for exosome-loading
ligation binding peptide		 1. untreated (PBS) NR 100 μL i.v. every 3 days (6 doses) 18 days
2. DOX 5 mg/kg 100 μL i.v. every 3 days (6 doses) 18 days
3. PL-D (5 mg/kg DOX) NR 100 μL i.v. every 3 days (6 doses) 18 days
4. EP-D (5 mg/kg DOX) NR 100 μL i.v. every 3 days (6 doses) 18 days
5. MEP-D (5 mg/kg DOX) NR 100 μL i.v. every 3 days (6 doses) 18 days
Jung et al.44 2018 SPIO-labeled Olaparib-loaded exosome incubation for SPIO and electroporation for Olaparib 1. untreated (PBS) NR NR i.t. every 2 days 3 weeks
2. Olaparib-loaded exosome 100 μg/mL NR i.t. every 2 days 3 weeks
3. Olaparib 100 μM NR i.t. every 2 days 3 weeks
Haney et al.45 2020 EV-PTX and EV-DOX sonication T11 models 1. EV-DOX (2.5 mg/kg DOX) 1 × 109 particles/100 μL/mouse 10 mL/kg i.v. days 1, 4, 7, 10, 14 19 days
2. EV-PTX (0.5 mg/kg PTX) 1 × 109 particles/100 μL/mouse 10 mL/kg i.v. days 1, 4, 7, 10, 14 19 days
3. EV 1 × 109 particles/100 μL/mouse 10 mL/kg i.v. days 1, 4, 7, 10, 14 19 days
4. Doxil (2.5 mg/kg DOX NR 10 mL/kg i.v. days 1, 4, 7, 10, 14 19 days
5. Taxol (0.5 mg/kg PTX) NR 10 mL/kg i.v. days 1, 4, 7, 10, 14 19 days
6. untreated (saline) NR 10 mL/kg i.v. days 1, 4, 7, 10, 14 19 days
MDA-MB-231 models 1. EV-DOX (2.5 mg/kg DOX) 1 × 109 particles/100 μL/mouse 10 mL/kg i.v. days 1, 4, 7, 10, 14 65 days
2. EV-PTX (0.5 mg/kg PTX) 1 × 109 particles/100 μL/mouse 10 mL/kg i.v. days 1, 4, 7, 10, 14 65 days
3. EV (exosome only) 1 × 109 particles/100 μL/mouse 10 mL/kg i.v. days 1, 4, 7, 10, 14 65 days
4. Doxil 2.5 mg/kg 10 mL/kg i.v. days 1, 4, 7, 10, 14 65 days
5. Taxol 0.5 mg/kg 10 mL/kg i.v. days 1, 4, 7, 10, 14 65 days
6. untreated (saline) NR 10 mL/kg i.v. days 1, 4, 7, 10, 14 65 days
Hadla et al.46 2016 Exo-DOX electroporation 1. untreated NR NR i.p. twice in week (5 doses) 16 days
2. DOX 3 mg/kg NR i.p. twice in week (5 doses) 16 days
3. Doxil (liposomal DOX, 6 mg/kg DOX) NR NR i.p. twice in week (5 doses) 16 days
4. ExoDOX (6 mg/kg DOX) NR NR i.p. twice in week (5 doses) 16 days
Gong et al.47 2019 Co-A15-Exo incubation 1. untreated (PBS) NR NR i.v. weekly 5 weeks
2. Exo NR NR i.v. weekly 5 weeks
3. cho-miR159 0.1 nmoL/kg NR i.v. weekly 5 weeks
4. DOX 5 mg/kg NR i.v. weekly 5 weeks
5. A.15 Exo NR NR i.v. weekly 5 weeks
6. A.15 Exo/cho-miR159 (0.1 nmoL/kg miR) NR NR i.v. weekly 5 weeks
7. A.15 Exo/DOX (5 mg/kg DOX) NR NR i.v. weekly 5 weeks
8. Co A15-Exo (0.1 nmoL/kg miR) and (5 mg/kg DOX) NR NR i.v. weekly 5 weeks
Gomari et al.48 2019 targeted exo-DOX cell engineering for targeted exosomes
electroporation for DOX loading		 1. untreated (PBS) NR NR i.v. twice in week (6 doses) NR
2. untargeted Exo-DOX 1.5 mg/kg NR i.v. twice in week (6 doses) NR
3. targeted Exo-DOX 1.5 mg/kg NR i.v. twice in week (6 doses) NR
4. free DOX 1.5 mg/kg NR i.v. twice in week (6 doses) NR
Feng et al.49 2021 DOX@Exo-PH20-FA cell engineering for Exox-PH20
incubation for FA coating
electroporation for DOX loading		 1. untreated (saline) NR NR i.v. days 7, 10, 13, 16, 19 22 days
2. free DOX NR NR i.v. days 7, 10, 13, 16, 19 22 days
3. DOX@Exos-Con (control) 100 μg DOX/200 μg total exosome protein NR i.v. days 7, 10, 13, 16, 19 22 days
4. DOX@Exos-PH20 100 μg DOX/200 μg total exosome protein NR i.v. days 7, 10, 13, 16, 19 22 days
5. DOX@Exo-PH20-FA 100 μg DOX/200 μg total exosome protein NR i.v. days 7, 10, 13, 16, 19 22 days
Cheng et al.50 2022 GEMINI-Exos cell engineering 1. untreated (PBS) NR NR i.v. every other day (6 doses) 50 days
2. exosomes 10 mg/kg NR i.v. every other day (6 doses) 50 days
3. PD-1-OX40LExos 10 mg/kg NR i.v. every other day (6 doses) 50 days
4. αCD3-αEGFR-Exos 10 mg/kg NR i.v. every other day (6 doses) 50 days
5. PD-1-OX40LExos + αCD3-αEGFR-Exos 10 mg/kg
for each		 NR i.v. every other day (6 doses) 50 days
6. αCD3-αEGFR-PD-1-OX40L GEMINI-Exos 10 mg/kg NR i.v. every other day (6 doses) 50 days
Nguyen Cao et al.51 2022 SBC-EV(ICG/PTX) incubation 1. untreated (PBS) NR NR i.v. day 0 14 days
2. PBS + US (3 min) NR NR i.v. day 0 14 days
3. ICG + PTX (10 mg/kg ICG + 0.4 mg/kg PTX) + US (3 min) 10 mg/kg ICG + 0.4 mg/kg PTX NR i.v. day 0 14 days
4. EV(ICG-PTX) (10 mg/kg ICG + 0.4 mg/kg PTX) + US (3 min) NR NR i.v. day 0 14 days
5. SBC-EV(ICG-PTX) (10 mg/kg ICG + 0.4 mg/kg PTX) + US (3 min) NR NR i.v. day 0 14 days
Ahmed et al.52 2015 PTEN-CT-loaded exosome cell engineering
electroporation		 into tail vein 1. exosome 150 μg NR i.v. NR 4 weeks
2. PTEN-CT-loaded exosome 150 μg NR i.v. NR 4 weeks
into tumor 1. exosome 150 μg NR i.t. NR 4 weeks
2. PTEN-CT-loaded exosome 150 μg NR i.t. NR 4 weeks
Hong et al.53 2019 Exo-PH20 cell engineering 1. PBS + 2 mg/kg anti-PD-L1 NR NR i.t. + i.p. every 3 days (3 doses) 18 days
2. Exo(control) + 2 mg/kg anti-PD-L1 50 μg NR i.t. + i.p. every 3 days (3 doses) 18 days
3. Exo-PH20 + 2 mg/kg anti-PD-L1 50 μg NR i.t. + i.p. every 3 days (3 doses) 18 days
Liu et al.54 2019 Exo-DVDMS-sonodynamic therapy incubation 1. control NR NR i.v. NR 12 days
2. US1 (2 W, 3 min) + US2 (3 W, 3 min) – – – NR 12 days
3. DVDMS 2 mg/kg NR i.v. NR 12 days
4. DVDMS + US1 2 mg/kg NR i.v. NR 12 days
5. DVDMS + US2 2 mg/kg NR i.v. NR 12 days
6. DVDMS + US1 + US2 2 mg/kg NR i.v. NR 12 days
7. Exo-DVDMS 2 mg/kg NR i.v. NR 12 days
8. Exo-DVDMS + US1 2 mg/kg NR i.v. NR 12 days
9. Exo-DVDMS + US2 2 mg/kg NR i.v. NR 12 days
10. Exo-DVDMS + US1 + US2 2 mg/kg NR i.v. NR 12 days
Melzer et al.55 2019 Taxol-loaded exosomes incubation 1. control exosomes NR 100 μL i.v. twice in week (6 doses) 21 days
2. Taxol exosomes NR 100 μL i.v. twice in week (6 doses) 21 days
3. Taxol 5 mg/kg 100 μL i.v. twice in week (6 doses) 21 days
Shi et al.56 2020 SMART-Exo cell engineering 1. PBS (control) NR NR i.v. every other days (6 doses) 33 days
2. αCD3-αHER2 SMART-Exos 1.5 × 1010 particles NR i.v. every other days (6 doses) 33 days
Usman et al.57 2018 125b-ASO-loaded RBCEVs electroporation 1. untreated – – i.t. every 3 days 44 days
2. UE-EVs 8.25 × 1011 particles NR i.t. every 3 days 44 days
3. NC-ASO E-EVs 8.25 × 1011 particles NR i.t. every 3 days 44 days
4. 125b-ASO E-EVs 8.25 × 1011 particles NR i.t. every 3 days 44 days
Wan et al.58 2018 AS1411-ENV-PTX ligation for AS141
sonication for PTX		 1. control NR NR i.v. every 2 days 21 days
2. ENV NR NR i.v. every 2 days 21 days
3. AS1411-ENV NR NR i.v. every 2 days 21 days
4. PTX 7.5 mg/kg NR i.v. every 2 days 21 days
5. ENV-PTX (7.5 mg/kg) NR NR i.v. every 2 days 21 days
6. AS1411-ENV-PTX (7.5 mg/kg) NR NR i.v. every 2 days 21 days
Wang et al.59 2017 AS1411-EV-let 7 miRNA ligation for AS141
electroporation for miRNA		 1. PBS (control) NR NR i.v. every other day 25 days
2. let-7 NR NR i.v. every other day 25 days
3. EVs 150 μg NR i.v. every other day 25 days
4. T-AS1411 NR NR i.v. every other day 25 days
5. AS1411-EVS 150 μg NR i.v. every other day 25 days
6. EVs-let-7 150 μg NR i.v. every other day 25 days
7. AS1411-EVs-let-7 150 μg NR i.v. every other day 25 days
Xiong et al.60 2019 NPs/Rex nanoprecipitation process for NPs
sonication for loading into Rex		 1. PBS (control) NR NR i.v. once a week 28 days
2. Rex NR NR i.v. once a week 28 days
3. Pt(lau)HSA NPs (4.55 mg/kg Pt) NR NR i.v. once a week 28 days
4. NPs/Rex (4.55 mg/kg Pt) NR NR i.v. once a week 28 days
5. HSA NR NR i.v. once a week 28 days
6. cisplatin 4.55 mg/kg NR i.v. once a week 28 days

Ctrl-VHH-immRNA, control exosome containing VHH antibody and immRNA; ENV, extracellular nanovesicle; Exo-DEPT, exosome-delivered enzyme prodrug therapy; DOX@Exo-PH20-FA, exosome express PH20 and modified by FA containing doxorubicin; EP-D, exosome-loaded PLGA and DOX; Exo-DVDMS, exosomes loaded by sinoporphyrin sodium; MSC-NTC, non-transfected mesenchymal stem cells; MEP-D, membrane-coated exosome-loaded PLGA and DOX; NPs/Rex, nanoparticle loaded into RAW-derived exosomes; NC-ASO E-EVs, negative control anti-sense oligonucleotide loaded into electroporated EVs; UE-EVs, un-electroporated EVs; US, ultrasound.