Exosomes are phospholipid-based particles endogenously produced by both normal and tumor cells. Initially identified as a pathway for shuttling cellular waste, for a long time they were thought to act as “garbage bags”, and only in the past few years have they emerged as a promising drug delivery system. In this review, we provide an overview of the knowledge about exosome architecture and biogenesis and the recent progress in isolation methods. Furthermore, we describe the mechanisms involved in both extra- and intracellular communication with a focus on glioma brain tumors. Glioma is considered a rare disease and is the most prominent aggressive brain malignancy. How exosomes target glial tumoral cells in vivo remains largely unknown. However, they are able to influence numerous physio-pathological aspects. Here, we discuss the role they play in this heterogeneous and complex microenvironment and their potential applications.

The combination of different imaging modalities can allow obtaining simultaneously morphological and functional information providing a more accurate diagnosis. This advancement can be reached through the use of multimodal tracers, and nanotechnology-based solutions allow the simultaneous delivery of different diagnostic compounds moving a step towards their safe administration for multimodal imaging acquisition. Among different processes, nanoprecipitation is a consolidate method for the production of nanoparticles and its implementation in microfluidics can further improve the control over final product features accelerating its potential clinical translation. A Hydrodynamic Flow Focusing (HFF) approach is proposed to produce through a ONE-STEP process Multimodal Pegylated crosslinked Hyaluronic Acid NanoParticles (PEG-cHANPs). A monodisperse population of NPs with an average size of 140 nm is produced and Gd-DTPA and ATTO488 compounds are co-encapsulated, simultaneously. The results showed that the obtained multimodal nanoparticle could work as MRI/Optical imaging probe. Furthermore, under the Hydrodenticity effect, a boosting of the T1 values with respect to free Gd-DTPA is preserved. Multimodal Imaging is a promising approach that allows the combination of different imaging techniques, overcoming limitations proper of every single modality 1,2. For example, recently, Magnetic Resonance Imaging (MRI) and Optical imaging (OI) have been used in combination to obtain the excellent sensitivity of the OI with the high spatial resolution of the MRI 3-5. Image acquisition can occur at different times (asynchronously) requiring post-processing analyses performed through digital image manipulation techniques; however, the best consistency both in time and space is achieved when images are simultaneously acquired (synchronously) 6. Despite the great advantages in the Hardware developments, probes able to support simultaneous acquisitions are still missing. Indeed, in current clinical practice, a cocktail of diagnostic compounds is injected with extremely high risk for the patient. In this scenario, the possibility to efficiently co-deliver through a single vector, different diagnostic compounds for different imaging modalities represents a key point. This challenge can be adequately tackled by applying nanotechnologies to the medical field 7-9. Indeed, nanosystems can be used as vectors of active agents and their composition, size, shape, and surface chemistry can be finely modulated to obtain the simultaneous delivery of multiple diagnostic compounds with a significant impact on an early and accurate diagnosis 10-12. Nanovectors can provide simultaneous visualization of the diseased site through different innovative imaging techniques, enhanced-circulation time for the diagnostic compounds, controlled release kinetics, and superior dose scheduling for improved patient compliance 13. However, when systemically injected, nanoparticles are immediately sequestered by macrophages