An update of nanoparticle-based approaches for glioblastoma multiforme immunotherapy.

Glioblastoma multiforme is a serious medical issue in the brain oncology field due to its aggressiveness and recurrence. Immunotherapy has emerged as a valid approach to counteract the growth and metastasization of glioblastoma multiforme. Among the different innovative approaches investigated, nanoparticles gain attention because of their versatility which is key in allowing precise targeting of brain tumors and increasing targeted drug delivery to the brain, thus minimizing adverse effects. This article reviews the progress made in this field over the past 2 years, focusing on nonspherical and biomimetic particles and on vectors for the delivery of nucleic acids. However, challenges still need to be addressed, considering the improvement of the particles passage across the blood-meningeal barrier and/or the blood-brain barrier, promoting the clinical translatability of these approaches.

Protein-functionalized nanoparticles derived from end-functional polymers and polymer prodrugs for crossing the blood-brain barrier.

Nanoparticles may provide a viable way for neuroprotective drugs to cross the blood-brain barrier (BBB), which limits the passage of most drugs from the peripheral circulation to the brain. Heterotelechelic polymer prodrugs comprising a neuroprotective model drug (adenosine) and a maleimide functionality were synthesized by the "drug-initiated" approach and subsequent nitroxide exchange reaction. Nanoparticles were obtained by nanoprecipitation and exhibited high colloidal stability with diameters in the 162-185 nm range and narrow size distributions. Nanoparticles were then covalently surface-conjugated to different proteins (albumin, α2-macroglobulin and fetuin A) to test their capability of enhancing BBB translocation. Their performances in terms of endothelial permeability and cellular uptake in an in vitro BBB model were compared to that of similar nanoparticles with surface-adsorbed proteins, functionalized or not with the drug. It was shown that bare NPs (i.e., NPs not surface-functionalized with proteins) without the drug exhibited significant permeability and cellular uptake, which were further enhanced by NP surface functionalization with α2-macroglobulin. However, the presence of the drug at the polymer chain-end prevented efficient passage of all types of NPs through the BBB model, likely due to adecrease in the hydrophobicity of the nanoparticle surface and alteration of the protein binding/coupling, respectively. These results established a new and facile synthetic approach for the surface-functionalization of polymer nanoparticles for brain delivery purposes.

The ability of liposomes, tailored for blood-brain barrier targeting, to reach the brain is dramatically affected by the disease state.

AIM: To investigate if and how the ability of liposomes, previously designed for Alzheimer's therapy, to reach the brain changes in aging/pathological conditions with respect to the healthy state. METHODS: Biodistribution and pharmacokinetics of liposomes in young or aged healthy mice and in an Alzheimer's mouse model were measured by radiochemical techniques. The expression of brain receptors and structural proteins was evaluated by Western blot. RESULTS: At equal blood levels, the amount and integrity of liposomes in the brain were dramatically lower in Alzheimer's or aged mice, with respect to young animals. These differences are likely attributable to molecular alterations in the brain vasculature. CONCLUSION: Brain alterations in pathology or aging should be considered in the design of drug delivery systems for brain targeting.