Lipid nanoparticles for RNA delivery: Self-assembling vs driven-assembling strategies.

Among non-viral vectors, lipid nanovectors are considered the gold standard for the delivery of RNA therapeutics. The success of lipid nanoparticles for RNA delivery, with three products approved for human use, has stimulated further investigation into RNA therapeutics for different pathologies. This requires decoding the pathological intracellular processes and tailoring the delivery system to the target tissue and cells. The complexity of the lipid nanovectors morphology originates from the assembling of the lipidic components, which can be elicited by various methods able to drive the formation of nanoparticles with the desired organization. In other cases, pre-formed nanoparticles can be mixed with RNA to induce self-assembly and structural reorganization into RNA-loaded nanoparticles. In this review, the most relevant lipid nanovectors and their potentialities for RNA delivery are described on the basis of the assembling mechanism and of the particle architecture.

Melanoma-derived exosomes: Versatile extracellular vesicles for diagnosis, metastasis, immune modulation, and treatment of melanoma.

Malignant melanoma is one of the most aggressive human neoplasms responsible for the majority of skin cancer-related deaths in its advanced stages. Achieving a thorough knowledge of reliable tumor-originated biomarkers and molecular mechanisms can provide many practical approaches and guide the way towards the design of rational curative therapies to improve the survival rate of patients. Cancer cells, including melanoma cells, release high amounts of a broad family of nanovesicles, containing different biochemical messages. Exosomes are a type of extracellular vesicles (EVs) that are generated by different cell populations and participate in the intercellular communication of surrounding and distant cells/tissues. Exosome cargo consists of several biologically active proteins and genomic components. Tumor cells tend to release exosomes throughout the tumor microenvironment, which affects the biological performance of recipient cells. Recent evidence provides new perspective in melanoma management, showing that melanoma-derived exosomes (MEXs) may represent a valuable tool for melanoma diagnosis and treatment. This review presents a summary of the potential role of MEXs in the early diagnosis of melanoma. More importantly, we also discuss the capacity of MEXs in reproducing numerous tumor-related functions required for angiogenesis, immune system modulation, induction of migration and metastatic spread, tumor chemotherapy resistance, and melanoma tumor progression and survival. Considering the advent of novel bioengineering and immunotherapy approaches, natural exosomes can be exerted as nanocarriers and cancer vaccines to facilitate the conduction of more efficient cancer treatment.

Nanocarriers Call the Last Shot in the Treatment of Brain Cancers.

Our brain is protected by physio-biological barriers. The blood-brain barrier (BBB) main mechanism of protection relates to the abundance of tight junctions (TJs) and efflux pumps. Although BBB is crucial for healthy brain protection against toxins, it also leads to failure in a devastating disease like brain cancer. Recently, nanocarriers have been shown to pass through the BBB and improve patients' survival rates, thus becoming promising treatment strategies. Among nanocarriers, inorganic nanocarriers, solid lipid nanoparticles, liposomes, polymers, micelles, and dendrimers have reached clinical trials after delivering promising results in preclinical investigations. The size of these nanocarriers is between 10 and 1000 nm and is modified by surface attachment of proteins, peptides, antibodies, or surfactants. Multiple research groups have reported transcellular entrance as the main mechanism allowing for these nanocarriers to cross BBB. Transport proteins and transcellular lipophilic pathways exist in BBB for small and lipophilic molecules. Nanocarriers cannot enter via the paracellular route, which is limited to water-soluble agents due to the TJs and their small pore size. There are currently several nanocarriers in clinical trials for the treatment of brain cancer. This article reviews challenges as well as fitting attributes of nanocarriers for brain tumor treatment in preclinical and clinical studies.