The effective delivery of target-specific siRNA to the brain by exploiting the exosomes derived from dendritic cells renders the paradigm shift for the prospective use of nanosized exosomes as a delivery system. Although the in vivo targeting strategies by other nanovesicles like liposomes exist, still this novel exosome-based delivery approach holds an inclusive dominance of in vivo security and reduced immunogenicity. Achieving promising exosome-based delivery strategies warrants more desirable exploration of their biology. Over the years, the invention of novel production, characterization, targeting strategies, and cargo loading techniques of exosome improved its ability to reach clinics. Essentially, exosomebased delivery of therapeutics assures to conquer the major hurdles, like delivery of cargos across impermeable biological barriers, like the blood−brain barrier, biocompatibility, increased solubility, metabolic stability, improved circulation time, target specific delivery, and pharmacokinetics, and thereby enhanced the efficacy of loaded therapeutic agents. In this article, we cover the current status of exosome as a delivery vehicle for therapeutics and the challenges that need to be overcome, and we also discuss future perspectives of this exciting field of research to transform it from bench to clinical reality.

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Although there is a strong correlation between multinucleated cells (MNCs) and cancer chemo-resistance in variety of cancers, our understanding of how multinucleated cells modulate the tumor micro-environment is limited. We captured multinucleated cells from triple-negative chemo-resistant breast cancers cells in a time frame, where they do not proliferate but rather significantly regulate their micro-environment. We show that oxidatively stressed MNCs induce chemo-resistance in vitro and in vivo by secreting VEGF and MIF. These factors act through the RAS/MAPK pathway to induce chemo-resistance by upregulating anti-apoptotic proteins. In MNCs, elevated reactive oxygen species (ROS) stabilizes HIF-1α contributing to increase production of VEGF and MIF. Together the data indicate, that the ROS-HIF-1α signaling axis is very crucial in regulation of chemo-resistance by MNCs. Targeting ROS-HIF-1α in future may help to abrogate drug resistance in breast cancer.

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