However, the potential risk of therapeutic lentiviral vectors is due to their intrinsic nature to integrate themselves into the human genome. nucleic acid (LNA)- altered anti-miRNAs [150]. However, a remaining challenge is the successful delivery of these therapeutic molecules to specific tissue and cells. Indeed, given the pleiotropic role of miRNAs and their ability to function in a cell type-dependent manner, the design of an effective delivery system is critical to guarantee tissue and cell specificity in order to reduce the risk of toxicity and side effects. Different types of biodegradable and biocompatible miRNA service providers have been synthesized as biodegradable and biocompatible, including liposomes, nanoparticles, polymers and viral brokers. The versatility of liposomal service providers made them suitable vehicles for co-delivery of miRNAs and small-molecule drugs, which concurrently are able to target the same malignancy cell, in an effective synergistic antitumor way. Liposomal service providers were firstly employed for siRNA and small standard drugs delivery in clinical trials. A liposomal formulation of a mimic of the tumor-suppressive miR-34 was first characterized in animal model of liver malignancy [150] and recently reached clinical development. Recently, another miR-34 mimic joined phase I clinical trials for the treatment of advanced hepatocarcinoma [149] (Table 3). Studies have also investigated the use in clinics of viral-based delivery systems [152]. In particular, lentiviral vectors DL-alpha-Tocopherol methoxypolyethylene glycol succinate made up of antagomiRs against miR-494 have been shown to reduce tumor-infiltrating MDSCs and their protumor activity in an in vivo model of breast cancer [82]. However, the potential risk of therapeutic lentiviral vectors is due to their intrinsic nature to integrate themselves into the human genome. To bypass this risk, adenoviruses and adeno-associated viruses might be more suitable for therapeutic purposes, due to their non-integrative activity. However, limits in large-scale production as well as the immunogenic potential DL-alpha-Tocopherol methoxypolyethylene glycol succinate still remain major issues in their effective and safe use in therapy. Therefore, non-viral delivery strategies have received more interest. In particular, cell-derived exosomes made up of immune-related miRNAs have the potential to be employed as therapeutic agents. Accordingly, exosome- and immune cell-based delivery represent two interesting potential strategies for miRNA-based malignancy immunotherapy. The use of tumor-derived extracellular vesicles to bHLHb38 deliver therapeutic miRNAs was recently reported, wherein the authors explained the efficient delivery of the tumor suppressive miRNA let-7a to epidermal growth factor receptor (EGFR)-expressing breast malignancy cells in vivo. However, the DL-alpha-Tocopherol methoxypolyethylene glycol succinate use of exosomes as miRNAs vehicles in malignancy therapies is only at the beginning and needs to be further investigated. Possible strategies to improve target selectivity are the modification of the vesicular membrane with ligands or antibodies targeted to the endogenous receptors of tumor or stromal cells. In this context, the combination of miRNA-related immunotherapy with standard cytotoxic drug brokers or targeted therapy would represent a valuable opportunity for effective therapeutic interventions in human malignancies. 8. Conclusions The prominent role of miRNAs as molecular determinants of the innate immune response qualifies them as novel potential therapeutic agents that could critically modulate the fine balance of innate immune cells involved in cancer progression. Acknowledgments The author thanks K.C. Pels for his help in editing and proofreading the paper. Conflicts of Interest The author declares no discord of interest..