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Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host's defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Moghaddam, Behzadi, Sedighian, Goleij, Kachuei, Heiat and Fooladi.)

Exosomes are biological nanoparticles (30-150 nm) secreted in the extracellular area from all of cells, that mediate intercellular message. Exosomes act as the carriers for numerous proteins, DNAs, RNAs and cell-signaling molecules. Therefore, exosomes secreted by the tumor cells are useful for diagnostic purposes because of their persistent presence in the blood and their provision of genetic cargo similar to those in tumor. Due to the risks of aggressive activity and ambiguity of biological activity in other tissues, the use of exosomes in drug delivery and imaging has been limited. However, their high loading, stability and longer circulation time, excellent targeting, high cell penetration performance, and optimal biodegradability have made them potential agents in targeted cancer treatment. Therefore, in addition to examining methods for isolating and loading exosomes, this paper discusses the applications of exosomes in biological measurement, imaging, and therapeutic activities. Also, this review describes the challenges of using exosomes compared to conventional methods and shows that it is very useful to use them due to less aggressive activities. Finally, this review attempts to provide an appropriate incentive by showing the performance of exosomes in cancer therapy through targeted drug delivery, gene therapy, imaging and diagnosis., (Copyright © 2020. Published by Elsevier Masson SAS.)

Targeted immune therapies are a modern approach to harness the immunity to treat cancer patients. Exosomes (EXOs) are nano-vesicles used for drug delivery in cancer treatment. We aimed to assess the effectiveness of novel designed EXO structures for immunotherapy alone and in combination with other components in animal models. EXO derived from untreated macrophage (EXO), WEHI-164 cell lysate treated EXO (EXO Lys ), HSP70 enriched WEHI-164 cell lysate treated EXO (EXO HSP70 ), Naloxone (NLX) treated EXO (EXO NLX ), Propranolol (PRP) treated EXO (EXO PRP ) and staphylococcal enterotoxin B (SEB) anchored to three kinds of EXOs designated as EXO/SEB, EXO Lys /SEB, EXO HSP70 /SEB were purified from J774 cell line. To determine the therapeutic effect of these novel constructed nano-vesicles, the animals were immunized with different types of EXOs at weekly intervals for three consecutive weeks and in the fourth week the WEHI-164 tumor cells were injected. Finally, the splenocyte proliferation was examined by MTT assay and tumor growth was also determined in each group. We observed that EXO HSP was more effective than EXO and EXO Lys to decrease the number of tumor cells and to stimulate immune responses in animal models (P < 0.05). In SEB-anchored EXO group, EXO HSP70 /SEB has the potency to stimulate immune responses more efficiently than EXO/SEB and EXO Lys /SEB and the tumor was not palpable until 28th day which may refer to synergistic effect of HSP70 and SEB on immunity. In EXO NLX treated mice proliferative response decreased significantly compared to control group (P > 0.05) and the tumor number was constant within a period of 28 days and EXO PRP may delay the occurrence of the fibrosarcoma tumor; After development of fibrosarcoma the number of tumors diminished over the studied period of time. Our results demonstrate that HSP70 enriched EXO is an effective immunoadjuvant in cancer immunotherapy and causes tumor regression in animal model., (Copyright © 2017 Elsevier Ltd. All rights reserved.)