Muscular Dystrophies (MDs) are a group of rare inherited genetic muscular pathologies encompassing a variety of clinical phenotypes, gene mutations and mechanisms of disease. MDs undergo progressive skeletal muscle degeneration causing severe health problems that lead to poor life quality, disability and premature death. There are no available therapies to counteract the causes of these diseases and conventional treatments are administered only to mitigate symptoms. Recent understanding on the pathogenetic mechanisms allowed the development of novel therapeutic strategies based on gene therapy, genome editing CRISPR/Cas9 and drug repurposing approaches. Despite the therapeutic potential of these treatments, once the actives are administered, their instability, susceptibility to degradation and toxicity limit their applications. In this frame, the design of delivery strategies based on nanomedicines holds great promise for MD treatments. This review focuses on nanomedicine approaches able to encapsulate therapeutic agents such as small chemical molecules and oligonucleotides to target the most common MDs such as Duchenne Muscular Dystrophy and the Myotonic Dystrophies. The challenge related to in vitro and in vivo testing of nanosystems in appropriate animal models is also addressed. Finally, the most promising nanomedicine-based strategies are highlighted and a critical view in future developments of nanomedicine for neuromuscular diseases is provided.

The main step in the assessment of nanomaterial safety and suitability for biomedical use is the location and the dynamic tracking of nanoparticles (NPs) inside cells or tissues. To precisely investigate the uptake mechanisms and intracellular fate of NPs, transmission electron microscopy is the technique of choice; however, the detection of NPs may sometimes be problematic. In fact, while NPs containing strongly electron dense (e.g., metal) components do not require specific detection methods at the ultrastructural level, organic NPs are hardly detectable in the intracellular environment due to their intrinsic moderate electron density. In this study, the critical-electrolyte-concentration Alcian Blue method set up by Schofield et al. in 1975 was applied to track hyaluronic-acid-based NPs in muscle cells in vitro. This long-established histochemical method proved to be a powerful tool allowing to identify not only whole NPs while entering cells and moving into the cytoplasm, but also their remnants following lysosomal degradation and extrusion.

Graphical Reactive oxygen species (ROS) are important signaling molecules that play key roles in the progression of inflammatory disorders. Owing to a mismatch of the antioxidant level to balance the overproduction of ROS, the induced chronic inflammation can lead to several type of diseases such as cancer, inflammatory bowel disease, atherosclerosis, diabetes or neurodegenerative disorders. Over the last years, nanomedicine has shown tremendous promise in ROS-regulating approaches. The development of advanced redox-active nanomaterials opened the range of possibilities to anti-inflammatory therapies, with the production of ROS-responsive nanosystems enabling targeted drug delivery or with the manufacture of ROS-scavenging nanomaterials reducing ROS excess levels. This review summarizes the latest developments and novel designs of ROS-based nanomedicines and discusses their therapeutical strategies and applications.

Glioblastoma multiforme (GBM) is characterized by a highly immunosuppressive tumor microenvironment (TME), posing significant challenges for efficient therapy's outcomes. Nanomedicine combined with immunotherapy holds the potential to modulate the TME and reactivate immune responses. This study proposes a polymeric nanosystem (NPs) encapsulating diaminocyclohexane-platinum II (DACHPt), an oxaliplatin derivative, to induce immunogenic cell death (ICD) in GBM cells. An ionic-gelation technique was employed to generate polymeric nanoparticles (NPs) with an approximate size of 200 nm. NPs internalization was analyzed in GBM cell lines, in vitro-derived macrophages, and in leukocytes and tumor cells from GBM patient via flow cytometry and confocal imaging. ICD was assessed by measuring two of its main markers: adenosine triphosphate (ATP) and high-mobility group box 1 (HMGB1). NPs were efficiently incorporated by myeloid and tumor cells, but not by lymphocytes. DACHPt-loaded NPs demonstrated enhanced cytotoxicity compared to free drug, with increased ATP and HMGB1 release from GBM cells, confirming ICD induction. Our findings suggest that DACHPt-loaded NPs represent a promising therapeutic strategy capable of targeting both tumor cells and tumor-promoting immune cells while inducing ICD.