Engineered exosomes delivering specific tumor-suppressive RNAi attenuate oral cancer progression

Abstract

Exosomes are involved in a wide range of biological processes in human cells. Considerable evidence suggests that engineered exosomes (eExosomes) containing therapeutic agents can attenuate the oncogenic activity of human cancer cells. Despite its biomedical relevance, no information has been available for oral squamous cell carcinoma (OSCC), and therefore the development of specific OSCC-targeting eExosomes (octExosomes) is urgently needed. We demonstrated that exosomes from normal fibroblasts transfected with Epstein–Barr Virus Induced-3 (EBI3) cDNA were electroporated with siRNA of lymphocyte cytoplasmic protein 1 (LCP1), as octExosomes, and a series of experiments were performed to evaluate the loading specificity/effectiveness and their anti-oral cancer cell activities after administration of octExosomes. These experiments revealed that octExosomes were stable, effective for transferring siLCP1 into OSCC cells and LCP1 was downregulated in OSCC cells with octExosomes as compared with their counterparts, leading to a significant tumor-suppressive effect in vitro and in vivo. Here we report the development of a new valuable tool for inhibiting tumor cells. By engineering exosomes, siLCP1 was transferred to specifically suppress oncogenic activity of OSCC cells. Inhibition of other types of human malignant cells merits further study.

Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastoma

“…Thus it is necessary to find suitable carriers for the effective delivery of siRNA in vivo (Ruan et al, 2018). Examinations confirmed the effectiveness of liposomal, viral vectors and nanoparticles for RNA transfection, while they are immunogenic, toxic and degrade slowly (Kase et al, 2021).…”

Research status and future prospects of extracellular vesicles in primary Sjögren’s syndrome

“…In addition, exosomes have become a promising drug delivery system to target specific areas because of their safety, low immunogenicity, high compatibility, and long half-lives. Some chemicals, proteins, and antibodies have been modified on the surface of exosomes to build a targeted and multifunctional biological drug delivery system for enhanced therapy [ 75 , 76 ]. The research scenario on EVs in pSS is summarized in Table 1 .…”

Therapeutic Potential of Nucleic Acids when Combined with Extracellular Vesicles

“…Initially designed to disrupt the cellular membrane for transfection by creating small pores for cargo to enter, electroporation has been used to load nucleic acids into EVs secreted from murine dendritic cell, HEK293T bovine milk, N2A, red blood cells, fiboblasts among others [ 29 , 31 , 61 , 121 - 123 ]. Electroporation functions by passing volts through the isolated EVs in suspension to form small pores in the lipid bilayer allowing for entry/exit of cargo [ 124 ].…”

“…EVs with targeting peptides for lung cancer cells displayed a 20% encapsulation efficiency with electroporation and notable gene silencing effect in vitro [ 125 ]. More recently, EVs from fibroblasts transfected with Epstein Barr Virus induced cDNA were electroporated with siRNA resulting in significant in vitro and in vivo tumor-suppressive effects [ 123 ]. Another study assessed electroporation in red blood cell EVs, using antisense oligonucleotides, Cas9 mRNA, and plasmid DNA cargos.…”