Engineered Extracellular Vesicles: A New Approach for Targeted Therapy of Tumors and Overcoming Drug Resistance

Overview

Journal Cancer Commun (Lond)

Publisher Wiley

Specialty Oncology

Date 2023 Dec 29

PMID 38155418

Authors

Chen Ming-Kun

Chen Zi-Xian

Cai Mao-Ping

Chen Hong

Chen Zhuang-Fei

Zhao Shan-Chao

Affiliations

Soon will be listed here.

Abstract

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.

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References

Hu S, Ma J, Su C, Chen Y, Shu Y, Qi Z . Engineered exosome-like nanovesicles suppress tumor growth by reprogramming tumor microenvironment and promoting tumor ferroptosis. Acta Biomater. 2021; 135:567-581. DOI: 10.1016/j.actbio.2021.09.003. View

Kara G, Calin G, Ozpolat B . RNAi-based therapeutics and tumor targeted delivery in cancer. Adv Drug Deliv Rev. 2022; 182:114113. DOI: 10.1016/j.addr.2022.114113. View

Zhang H, Wang Y, Bai M, Wang J, Zhu K, Liu R . Exosomes serve as nanoparticles to suppress tumor growth and angiogenesis in gastric cancer by delivering hepatocyte growth factor siRNA. Cancer Sci. 2017; 109(3):629-641. PMC: 5834801. DOI: 10.1111/cas.13488. View

Haubner R, Wester H, Burkhart F, Senekowitsch-Schmidtke R, Weber W, Goodman S . Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med. 2001; 42(2):326-36. View

Akao Y, Iio A, Itoh T, Noguchi S, Itoh Y, Ohtsuki Y . Microvesicle-mediated RNA molecule delivery system using monocytes/macrophages. Mol Ther. 2010; 19(2):395-9. PMC: 3034851. DOI: 10.1038/mt.2010.254. View

Parrales A, Iwakuma T . Targeting Oncogenic Mutant p53 for Cancer Therapy. Front Oncol. 2016; 5:288. PMC: 4685147. DOI: 10.3389/fonc.2015.00288. View

Nie H, Xie X, Zhang D, Zhou Y, Li B, Li F . Use of lung-specific exosomes for miRNA-126 delivery in non-small cell lung cancer. Nanoscale. 2019; 12(2):877-887. DOI: 10.1039/c9nr09011h. View

Dar G, Mendes C, Kuan W, Speciale A, Conceicao M, Gorgens A . GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain. Nat Commun. 2021; 12(1):6666. PMC: 8602309. DOI: 10.1038/s41467-021-27056-3. View

Grainger D . Connecting drug delivery reality to smart materials design. Int J Pharm. 2013; 454(1):521-4. DOI: 10.1016/j.ijpharm.2013.04.061. View

10.

Barile L, Vassalli G . Exosomes: Therapy delivery tools and biomarkers of diseases. Pharmacol Ther. 2017; 174:63-78. DOI: 10.1016/j.pharmthera.2017.02.020. View

11.

Thery C, Zitvogel L, Amigorena S . Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002; 2(8):569-79. DOI: 10.1038/nri855. View

12.

Daniels T, Bernabeu E, Rodriguez J, Patel S, Kozman M, Chiappetta D . The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta. 2011; 1820(3):291-317. PMC: 3500658. DOI: 10.1016/j.bbagen.2011.07.016. View

13.

Smyth T, Petrova K, Payton N, Persaud I, Redzic J, Graner M . Surface functionalization of exosomes using click chemistry. Bioconjug Chem. 2014; 25(10):1777-84. PMC: 4198107. DOI: 10.1021/bc500291r. View

14.

Lin Z, Wu Y, Xu Y, Li G, Li Z, Liu T . Mesenchymal stem cell-derived exosomes in cancer therapy resistance: recent advances and therapeutic potential. Mol Cancer. 2022; 21(1):179. PMC: 9468526. DOI: 10.1186/s12943-022-01650-5. View

15.

Jia G, Han Y, An Y, Ding Y, He C, Wang X . NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo. Biomaterials. 2018; 178:302-316. DOI: 10.1016/j.biomaterials.2018.06.029. View

16.

Tian T, Wang Y, Wang H, Zhu Z, Xiao Z . Visualizing of the cellular uptake and intracellular trafficking of exosomes by live-cell microscopy. J Cell Biochem. 2010; 111(2):488-96. DOI: 10.1002/jcb.22733. View

17.

Abumiya T, Lucero J, Heo J, Tagaya M, Koziol J, Copeland B . Activated microvessels express vascular endothelial growth factor and integrin alpha(v)beta3 during focal cerebral ischemia. J Cereb Blood Flow Metab. 1999; 19(9):1038-50. DOI: 10.1097/00004647-199909000-00012. View

18.

Qi H, Liu C, Long L, Ren Y, Zhang S, Chang X . Blood Exosomes Endowed with Magnetic and Targeting Properties for Cancer Therapy. ACS Nano. 2016; 10(3):3323-33. DOI: 10.1021/acsnano.5b06939. View

19.

Anand P, Thomas S, Kunnumakkara A, Sundaram C, Harikumar K, Sung B . Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Pharmacol. 2008; 76(11):1590-611. DOI: 10.1016/j.bcp.2008.08.008. View

20.

Chanmee T, Ontong P, Konno K, Itano N . Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel). 2014; 6(3):1670-90. PMC: 4190561. DOI: 10.3390/cancers6031670. View