Nucleic acids EVs are natural carriers of nucleic acids molecules and can be genetically engineered to deliver specific nucleic acid molecules such as siRNA (El-Andaloussi et?al., 2012), miRNA (Li et?al., 2019c), and gene editing system-CRISPER/Cas9 (Lin et?al., 2018). to lack of standardized isolation and purification methods, limited drug loading efficiency, and insufficient clinical grade production. In this review, we summarized the current knowledge on the application of EVs as DDS from the perspective of different cell origin and weighted the advantages and bottlenecks of EV-based DDS. replication (Gabrilovich et?al., 1996; Zhang et?al., 2014a). In the last decade, DEV-based therapy was not only launched in immunotherapy but also applied in drug delivery. The work initially described by Alvarez-Erviti et?al. (2011) in 2011 exhibited that DEVs can be developed for targeted RNA interference (RNAi) delivery to the brain after systemic injection using RVG-targeted exosomes. They provided the first proof-of-concept research for the potential of these naturally occurring vesicles for drug delivery. The next 12 months, El-Andaloussi et?al. (2012) provided a protocol that first described the generation of targeted exosomes through transfection of an expression vector. Next, they explained how to purify and characterize exosomes from transfected cell supernatant. Then, they detailed crucial steps for loading siRNA into exosomes and finally they outlined how to use exosomes to efficiently deliver siRNA and (Pullan et?al., 2019). According to the multiple applications of DEVs, we can conclude that DEVs are candidates for immunotherapy and drug delivery (Lakhal & Solid wood, 2011; Pitt et?al., 2016; Sabado et?al., 2017). The antigen-presenting molecules, MHC-I, II, and T cell co-stimulators are enriched in DEVs (Pitt et?al., 2016). Thus, for DDSs, DEVs will play dual effects of immunity and anti-tumor therapy in treatment of cancer (Pitt et?al., 2016). Moreover, DEVs can overcome the biological barriers, such as bloodCbrain barrier (BBB), making them more attractive in future drug delivery (Khan et?al., 2018). 3.1.2. Mesenchymal stem cells Mesenchymal stem cells (MSCs) and easily accessible primary cells can be harvested from a large variety of tissues (Lee et?al., 2004; Kern et?al., 2006), such as adipose tissue (Lee et?al., 2004; Banas et?al., 2007), umbilical cord blood (Kern et?al., 2006), liver (G?therstr?m et?al., 2003), amniotic fluid (Roubelakis et?al., 2007), and placenta (Miao et?al., 2006) as well as dental pulp (Huang et?al., 2009; Lai et?al., 2010). These cells can differentiate into both mesenchymal and non-mesenchymal cells (Sato et?al., 2011). The convenience of isolation and specialized biological functions of MSCs make them a popular choice for cell therapy in preclinical and clinical trials. Early in 2004, Nakamura et?al. (2004) initially described the antitumor effect of designed MSCs in a rat glioma model. Since then, there were emerging works that utilized MSCs in gene therapy and drug delivery (Kim et?al., 2010; Sun et?al., 2011; Hsiao et?al., 2012; Lee et?al., 2014; Choi et?al., 2015). Hu et?al. (2011) exhibited that human umbilical blood mononuclear cell-derived MSCs serve as interleukin-21 gene delivery vehicles for epithelial ovarian cancer therapy in nude mice. Pessina et?al. (2011) provided a new approach (+)-Penbutolol by MSCs primed with paclitaxel loading for cancer (+)-Penbutolol therapy loaded with paclitaxel. Thus, MSCs have been regarded as GRIA3 an ideal carrier for drug and gene delivery. Recently, it is proposed that MSCs might exert their therapeutic effects mainly through secreted extracellular factors (Wen et?al., 2016). As EVs (+)-Penbutolol are involved in cellCcell communication, it is hypothesized that EVs mediate the paracrine effects of MSCs (Mancuso et?al., 2019). MSC-derived EVs (MEVs) have been revealed to have comparable function of MSCs, such as facilitating the repair of kidney injury (Yao & Ricardo, 2016), modulating immune responses (Zhang et?al., 2014b), promoting wound healing (Gregoire et?al., 2015), and drug delivery (Lai et?al., 2013). Munoz et?al. (2013) reported.