Enhanced Therapeutic Potential of Hybrid Exosomes Loaded with Paclitaxel for Cancer Therapy

Xuan Wang; Dongdong Li; Gaotian Li; Jinda Chen; Yi Yang; Lijun Bian; Jingying Zhou; Yongge Wu; Yan Chen

doi:10.3390/ijms25073645

journal article Open Access Mar 25, 2024

Enhanced Therapeutic Potential of Hybrid Exosomes Loaded with Paclitaxel for Cancer Therapy

Xuan Wang

Dongdong Li

Gaotian Li Jinda Chen Yi Yang

Lijun Bian Jingying Zhou Yongge Wu Yan Chen

International Journal of Molecular Sciences Vol. 25 No. 7 pp. 3645 · MDPI AG

View at Publisher Save 10.3390/ijms25073645

Abstract

The advancement of exosome studies has positioned engineered exosomes as crucial biomaterials for the development of advanced drug delivery systems. This study focuses on developing a hybrid exosome system by fusing mesenchymal stem cells (MSCs) exosomes with folate-targeted liposomes. The aim was to improve the drug loading capacity and target modification of exosome nanocarriers for delivering the first-line chemotherapy drug paclitaxel (PTX) and its effectiveness was assessed through cellular uptake studies to evaluate its ability to deliver drugs to tumor cells in vitro. Additionally, in vivo experiments were conducted using a CT26 tumor-bearing mouse model to assess the therapeutic efficacy of hybrid exosomes loaded with PTX (ELP). Cellular uptake studies demonstrated that ELP exhibited superior drug delivery capabilities to tumor cells in vitro. Moreover, in vivo experiments revealed that ELP significantly suppressed tumor growth in the CT26 tumor-bearing mouse model. Notably, for the first time, we examined the tumor microenvironment following intratumoral administration of ELP. We observed that ELP treatment activated CD4+ and CD8+ T cells, reduced the expression of M2 type tumor-associated macrophages (TAMs), polarized TAMs towards the M1 type, and decreased regulatory T cells (Tregs). Our research highlights the considerable therapeutic efficacy of ELP and its promising potential for future application in cancer therapy. The development of hybrid exosomes presents an innovative approach to enhance drug delivery and modulate the tumor microenvironment, offering exciting prospects for effective cancer treatment strategies.

Topics

No keywords indexed for this article. Browse by subject →

References

29

[1]

Extracellular vesicles as drug delivery systems: Lessons from the liposome field

Roy van der Meel, Marcel H.A.M. Fens, Pieter Vader et al.

Journal of Controlled Release 2014 10.1016/j.jconrel.2014.07.049

[2]

Yeo "Mesenchymal stem cell: An efficient mass producer of exosomes for drug delivery" Adv. Drug Deliv. Rev. (2013) 10.1016/j.addr.2012.07.001

[3]

Vader "Extracellular vesicles for drug delivery" Adv. Drug Deliv. Rev. (2016) 10.1016/j.addr.2016.02.006

[4]

Liu "The biology, function, and applications of exosomes in cancer" Acta Pharm. Sin. B (2021) 10.1016/j.apsb.2021.01.001

[5]

The biology , function , and biomedical applications of exosomes

Raghu Kalluri, Valerie S. LeBleu

Science 2020 10.1126/science.aau6977

[6]

Liang "Engineering exosomes for targeted drug delivery" Theranostics (2021) 10.7150/thno.52570

[7]

Exosomes as drug delivery vehicles for Parkinson's disease therapy

Matthew J. Haney, Natalia L. Klyachko, Yuling Zhao et al.

Journal of Controlled Release 2015 10.1016/j.jconrel.2015.03.033

[8]

A Novel Nanoparticle Drug Delivery System: The Anti-inflammatory Activity of Curcumin Is Enhanced When Encapsulated in Exosomes

Dongmei Sun, Xiaoying Zhuang, Xiaoyu Xiang et al.

Molecular Therapy 2010 10.1038/mt.2010.105

[9]

Choi "Enhanced effect of autologous EVs delivering paclitaxel in pancreatic cancer" J. Control. Release (2022) 10.1016/j.jconrel.2022.05.012

[10]

Keshtkar "Mesenchymal stem cell-derived extracellular vesicles: Novel frontiers in regenerative medicine" Stem Cell Res. Ther. (2018) 10.1186/s13287-018-0791-7

[11]

Wang "Mesenchymal Stem Cell-Based Immunomodulation: Properties and Clinical Application" Stem Cells Int. (2018) 10.1155/2018/3057624

[12]

Ho "Human bone marrow-derived mesenchymal stem cells suppress human glioma growth through inhibition of angiogenesis" Stem Cells (2013) 10.1002/stem.1247

[13]

Hong "The functions and clinical application potential of exosomes derived from adipose mesenchymal stem cells: A comprehensive review" Stem Cell Res. Ther. (2019) 10.1186/s13287-019-1358-y

[14]

Zhu, L., and Chen, L. (2019). Progress in research on paclitaxel and tumor immunotherapy. Cell. Mol. Biol. Lett., 24. 10.1186/s11658-019-0164-y

[15]

Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential

Zhengjun Lin, Yanlin Wu, Yiting Xu et al.

Molecular Cancer 2022 10.1186/s12943-022-01650-5

[16]

Kodumudi "A Novel Chemoimmunomodulating Property of Docetaxel: Suppression of Myeloid-Derived Suppressor Cells in Tumor Bearers" Clin. Cancer Res. (2010) 10.1158/1078-0432.ccr-10-0733

[17]

Liu "Immunomodulatory Effects of Mesenchymal Stem Cells and Mesenchymal Stem Cell-Derived Extracellular Vesicles in Rheumatoid Arthritis" Front. Immunol. (2020)

[18]

Heo "Human Adipose Mesenchymal Stem Cell-Derived Exosomes: A Key Player in Wound Healing" Tissue Eng. Regen. Med. (2021) 10.1007/s13770-020-00316-x

[19]

Mansourabadi, A.H., Aghamajidi, A., Faraji, F., Taghizadeh, S., Mohamed Khosroshahi, L., Bahramkiya, M., and Azimi, M. (2022). Mesenchymal stem cells-derived exosomes inhibit the expression of Aquaporin-5 and EGFR in HCT-116 human colorectal carcinoma cell line. BMC Mol. Cell Biol., 23. 10.1186/s12860-022-00439-0

[20]

Wei "A Nanodrug Consisting Of Doxorubicin And Exosome Derived From Mesenchymal Stem Cells For Osteosarcoma Treatment In Vitro" Int. J. Nanomed. (2019) 10.2147/ijn.s218988

[21]

Kalimuthu "A New Approach for Loading Anticancer Drugs Into Mesenchymal Stem Cell-Derived Exosome Mimetics for Cancer Therapy" Front. Pharmacol. (2018) 10.3389/fphar.2018.01116

[22]

Bilotta "Managing the TME to improve the efficacy of cancer therapy" Front. Immunol. (2022) 10.3389/fimmu.2022.954992

[23]

Naito "CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer" Cancer Res. (1998)

[24]

Li "Tumor-associated macrophage infiltration and prognosis in colorectal cancer: Systematic review and meta-analysis" Int. J. Color. Dis. (2020) 10.1007/s00384-020-03593-z

[25]

Son "Distinct tumor immune microenvironments in primary and metastatic lesions in gastric cancer patients" Sci. Rep. (2020) 10.1038/s41598-020-71340-z

[26]

Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages

Xiang Ying, Quanfeng Wu, Xiaoli Wu et al.

Oncotarget 2016 10.18632/oncotarget.9246

[27]

Lou "Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma" J. Hematol. Oncol. (2015) 10.1186/s13045-015-0220-7

[28]

Sato "Engineering hybrid exosomes by membrane fusion with liposomes" Sci. Rep. (2016) 10.1038/srep21933

[29]

Paula "Suppression of the Hemolytic Effect of Mesoporous Silica Nanoparticles after Protein Corona Interaction: Independence of the Surface Microchemical Environment" J. Braz. Chem. Soc. (2012) 10.1590/s0103-50532012005000048

Cited By

38

Engineered Exosomes as Smart Drug Carriers: Overcoming Biological Barriers in CNS and Cancer Therapy

Tanvi Premchandani, Amol Tatode · 2025

Drugs and Drug Candidates

Metrics

38

Citations

29

References

Details

Published: Mar 25, 2024
Vol/Issue: 25(7)
Pages: 3645
License: View

Authors

X

Xuan Wang