# Exosomes as Drug Carriers in Anti-Cancer Therapy

**Authors:** Lan Chen, Li Wang, Lingling Zhu, Zihan Xu, Yanyang Liu, Zhixi Li, Jin Zhou, Feng Luo

PMC · DOI: 10.3389/fcell.2022.728616 · Frontiers in Cell and Developmental Biology · 2022-01-26

## TL;DR

Exosomes show promise as safe and effective drug carriers for cancer therapy due to their unique properties, but challenges like low yield and drug loading efficiency remain.

## Contribution

This paper reviews the current use and challenges of exosome-based drug delivery systems in cancer therapy.

## Key findings

- Exosomes offer low immunogenicity and high stability, making them suitable for drug delivery.
- Exosome-based systems can stimulate anti-cancer immune responses.
- Challenges include heterogeneity, low yield, and limited drug loading efficiency.

## Abstract

Over the years, there has been a high demand for developing new safe and effective drug carriers for cancer therapy. Emerging studies have indicated that exosomes can serve as potent therapeutic carriers since they offer low immunogenicity, high stability, innate and acquired targetability, and the stimulation of anti-cancer immune responses. Yet, the development of exosome-based drug delivery systems remains challenging due to their heterogeneity, low yield, and limited drug loading efficiency. Herein, we summarized the current application of exosomes derived from different cells as drug carriers in anti-cancer therapy in vitro and in vivo. We also discussed the challenges and prospects of exosome-based drug delivery systems in cancer therapy.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** VTN (vitronectin) [NCBI Gene 7448] {aka V75, VN, VNT}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, AFP (alpha fetoprotein) [NCBI Gene 174] {aka AFPD, FETA, HPAFP}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, NRP1 (neuropilin 1) [NCBI Gene 8829] {aka BDCA4, CD304, NP1, NRP, VEGF165R}, ITGB4 (integrin subunit beta 4) [NCBI Gene 3691] {aka CD104, GP150, JEB5A, JEB5B}, MIR204 (microRNA 204) [NCBI Gene 406987] {aka MIRN204, RDICC, miRNA204, mir-204}, HSP90AA1 (heat shock protein 90 alpha family class A member 1) [NCBI Gene 3320] {aka EL52, HEL-S-65p, HSP86, HSP89A, HSP90A, HSP90N}, TPD52 (tumor protein D52) [NCBI Gene 7163] {aka D52, N8L, PC-1, PrLZ, hD52}, ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) [NCBI Gene 25] {aka ABL, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, PDCD6IP (programmed cell death 6 interacting protein) [NCBI Gene 10015] {aka AIP1, ALIX, DRIP4, HP95, MCPH29}, Lamp2 (lysosomal-associated membrane protein 2) [NCBI Gene 16784] {aka CD107b, LGP-B, Lamp II, Lamp-2, Lamp-2a, Lamp-2b}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, Sox2 (SRY (sex determining region Y)-box 2) [NCBI Gene 20674] {aka Sox-2, lcc, ysb}, Mir206 (microRNA 206) [NCBI Gene 387202] {aka Mirn206, mmu-mir-206}, HSPA5 (heat shock protein family A (Hsp70) member 5) [NCBI Gene 3309] {aka BIP, GRP78, HEL-S-89n}, MIR223 (microRNA mir-223) [NCBI Gene 100315091] {aka eca-mir-223}, MIR379 (microRNA 379) [NCBI Gene 494328] {aka MIRN379, hsa-mir-379, mir-379}, RAB22A (RAB22A, member RAS oncogene family) [NCBI Gene 57403], HGF (hepatocyte growth factor) [NCBI Gene 3082] {aka DFNB39, F-TCF, HGFB, HPTA, SF}, Cd44 (CD44 antigen) [NCBI Gene 12505] {aka HERMES, Ly-24, Pgp-1}, MIR10B (microRNA 10b) [NCBI Gene 406903] {aka MIRN10B, hsa-mir-10b, miRNA10B, mir-10b}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, Cdh2 (cadherin 2) [NCBI Gene 12558] {aka CDHN, N-CAD, Ncad}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, MIR126 (microRNA 126) [NCBI Gene 406913] {aka MIRN126, miRNA126, mir-126}, LAMP2 (lysosome associated membrane protein 2) [NCBI Gene 3920] {aka CD107b, DND, LAMP-2, LAMPB, LGP-96, LGP110}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, TSG101 (tumor susceptibility 101) [NCBI Gene 7251] {aka TSG10, VPS23}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, Ifi47 (interferon gamma inducible protein 47) [NCBI Gene 15953] {aka 47kDa, IRG-47, Ifggc1, Igrd, Iigp4, Iipg4}, Lamp3 (lysosomal-associated membrane protein 3) [NCBI Gene 239739] {aka 1200002D17Rik, Cd208, DC-LAMP, DCLAMP, LAMP, TSC403}, CD82 (CD82 molecule) [NCBI Gene 3732] {aka 4F9, C33, GR15, IA4, KAI1, R2}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, Ptk7 (PTK7 protein tyrosine kinase 7) [NCBI Gene 71461] {aka 8430404F20Rik, chz, mPTK7/CCK4}, POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4}, CD81 (CD81 molecule) [NCBI Gene 975] {aka CVID6, S5.7, TAPA1, TSPAN28}, Kras (Kras proto-oncogene, GTPase) [NCBI Gene 16653] {aka K-Ras, K-Ras 2, K-ras, Ki-ras, Kras-2, Kras2}, RAB2A (RAB2A, member RAS oncogene family) [NCBI Gene 5862] {aka LHX, RAB2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, RAB7B (RAB7B, member RAS oncogene family) [NCBI Gene 338382] {aka RAB7}, TRIM3 (tripartite motif containing 3) [NCBI Gene 10612] {aka BERP, HAC1, RNF22, RNF97}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, Itgb4 (integrin beta 4) [NCBI Gene 192897] {aka C230078O20, CD104}, VIM (vimentin) [NCBI Gene 7431], MIR23B (microRNA 23b) [NCBI Gene 407011] {aka MIRN23B, hsa-mir-23b, miRNA23B, mir-23b}, Afp (alpha fetoprotein) [NCBI Gene 11576], HOXA@ (homeobox A cluster) [NCBI Gene 3197] {aka HOX1@}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, IL3 (interleukin 3) [NCBI Gene 3562] {aka IL-3, MCGF, MULTI-CSF}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}
- **Diseases:** vomiting (MESH:D014839), renal cancer (MESH:D007680), lung cancer (MESH:D008175), platelet aggregation (MESH:D001791), mitochondrial dysfunction (MESH:D028361), rheumatoid arthritis (MESH:D001172), prostate cancer (MESH:D011471), -stage cancer (MESH:D009369), osteosarcoma (MESH:D012516), NSCLC (MESH:D002289), breast cancer (MESH:D001943), cardiovascular toxicity (MESH:D002318), cytotoxicity (MESH:D064420), HCC (MESH:D006528), acute myeloid leukemia (MESH:D015470), death (MESH:D003643), Alzheimer's diseases (MESH:D000544), nasopharyngeal carcinoma (MESH:D000077274), cervical cancer (MESH:D002583), radiation dermatitis (MESH:D011855), multiple myeloma (MESH:D009101), radiation pneumonitis (MESH:D017564), glioma (MESH:D005910), colon cancer (MESH:D015179), fibrosarcoma (MESH:D005354), ovarian cancer (MESH:D010051), Crohn's disease (MESH:D003424), chronic myeloid leukemia (MESH:D015464), gastric cancer (MESH:D013274), melanoma (MESH:D008545), bladder cancer (MESH:D001749), pancreatic cancer (MESH:D010190), metastasis (MESH:D009362), cardiac toxicity (MESH:D066126), glioblastoma (MESH:D005909), degenerative diseases (MESH:D019636), graft-versus-host disease (MESH:D006086)
- **Chemicals:** poly (I:C) (MESH:D011070), water (MESH:D014867), withaferin A (MESH:C009684), DIR (-), ASOs (MESH:D016376), curcumin (MESH:D003474), vitamin D (MESH:D014807), 99mT c (MESH:D013667), 5-FU (MESH:D005472), triptolide (MESH:C001899), paclitaxel (MESH:D017239), cisplatin (MESH:D002945), DOX (MESH:D004317), phosphatidylcholine (MESH:D010713), sorafenib (MESH:D000077157), FA (MESH:D005492), gefitinib (MESH:D000077156), Texas Red (MESH:C034657), osimertinib (MESH:C000596361), lipid (MESH:D008055), hyaluronan (MESH:D006820), docetaxel (MESH:D000077143), talazoparib (MESH:C586365), CEL (MESH:C050414), calcium (MESH:D002118), Anthos (MESH:D000872)
- **Species:** Homo sapiens (human, species) [taxon 9606], Macropus sp. (kangaroo, species) [taxon 9322], Rattus norvegicus (brown rat, species) [taxon 10116], Sus scrofa (pig, species) [taxon 9823], Ovis aries (domestic sheep, species) [taxon 9940], Mus musculus (house mouse, species) [taxon 10090], Bos taurus (bovine, species) [taxon 9913]
- **Cell lines:** BM- — Homo sapiens (Human), Transformed cell line (CVCL_E481), Hepatoma 22 — Mus musculus (Mouse), Hepatocellular carcinoma of the mouse, Cancer cell line (CVCL_H613), C26 — Rattus norvegicus (Rat), Spontaneously immortalized cell line (CVCL_0507), MGC-803 — Homo sapiens (Human), Hybrid cell line (CVCL_5334), BT-474 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0179), T47D — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0553), SGC7901 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0520), CEM — Homo sapiens (Human), Childhood T acute lymphoblastic leukemia, Cancer cell line (CVCL_0207), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), Panc28 — Homo sapiens (Human), Pancreatic adenocarcinoma, Cancer cell line (CVCL_7666), MOLM13 — Homo sapiens (Human), Adult acute monocytic leukemia, Cancer cell line (CVCL_2119), HCT-1165FR — Homo sapiens (Human), Pancreatic carcinoma, Cancer cell line (CVCL_D135), HEK293 — Homo sapiens (Human), Transformed cell line (CVCL_0045), CT26 — Mus musculus (Mouse), Mouse colon adenocarcinoma, Cancer cell line (CVCL_7254), NOMO1 — Homo sapiens (Human), Adult acute monocytic leukemia, Cancer cell line (CVCL_1609), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), BM-MSC — Mus musculus (Mouse), Transformed cell line (CVCL_U446), A2780 — Homo sapiens (Human), Ovarian endometrioid adenocarcinoma, Cancer cell line (CVCL_0134), PLC-SR — Homo sapiens (Human), Adult hepatocellular carcinoma, Cancer cell line (CVCL_0485), SKOV3 — Homo sapiens (Human), Ovarian serous cystadenocarcinoma, Cancer cell line (CVCL_0532), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), HCT116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), NS0 — Mus musculus (Mouse), Mouse multiple myeloma, Cancer cell line (CVCL_3940), CA1a — Homo sapiens (Human), Head and neck squamous cell carcinoma, Cancer cell line (CVCL_A5TQ), HT-1080 — Homo sapiens (Human), Fibrosarcoma, Cancer cell line (CVCL_0317), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC8826094/full.md

## References

85 references — full list in the complete paper: https://tomesphere.com/paper/PMC8826094/full.md

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Source: https://tomesphere.com/paper/PMC8826094