Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments

Abstract

Glioblastoma Multiforme (GBM) is a devastating disease with a low survival rate and few efficacious treatment options. The fast growth, late diagnostics, and off-target toxicity of currently used drugs represent major barriers that need to be overcome to provide a viable cure. Nanomedicines (NMeds) offer a way to overcome these pitfalls by protecting and loading drugs, increasing blood half-life, and being targetable with specific ligands on their surface. In this study, the FDA-approved polymer poly (lactic-co-glycolic) acid was used to optimise NMeds that were surface modified with a series of potential GBM-specific ligands. The NMeds were fully characterised for their physical and chemical properties, and then in vitro testing was performed to evaluate cell uptake and GBM cell specificity. While all targeted NMeds showed improved uptake, only those decorated with the-cell surface vimentin antibody M08 showed specificity for GBM over healthy cells. Finally, the most promising targeted NMed candidate was loaded with the well-known chemotherapeutic, paclitaxel, to confirm targeting and therapeutic effects in C6 GBM cells. These results demonstrate the importance of using well-optimised NMeds targeted with novel ligands to advance delivery and pharmaceutical effects against diseased cells while minimising the risk for nearby healthy cells.

Recent Advances on Surface-Modified GBM Targeted Nanoparticles: Targeting Strategies and Surface Characterization

“…Moreover, a major apoptotic effect and cell death were observed for paclitaxel-loaded M08-NPs compared to nontargeted NPs or free paclitaxel. These results demonstrated the potential of this ligand to be a novel targeting candidate that could be conjugated onto a drug delivery platform for the treatment of GBM [40]. A major limitation to both the articles by Guo et al and Duskey et al is that all assays were only performed in vitro, and further in vivo analyses are needed to corroborate these results.…”

“Combo” Multi-Target Pharmacological Therapy and New Formulations to Reduce Inflammation and Improve Endogenous Remyelination in Traumatic Spinal Cord Injury

“…Cy5-labeled empty NMeds and Cy5-labeled T3-NMeds were prepared through the nanoprecipitation procedure described above with 49 mg of PLGA and 1 mg of PLGA-Cy5. The PLGA was conjugated to Cy5 through the formation of an amide bond, as described in an already published work [26].…”

Hyaluronic Acid Scaffolds for Loco-Regional Therapy in Nervous System Related Disorders

“…Other approved molecules for the treatment of GB include carmustine, lomustine and even monoclonal antibodies such as bevacizumab [ 30 ]. Another innovative approach is represented by nanomedicines; in fact, the particular tumor microenvironment and surface characteristics of GB cells allow for the specific targeting of drug-loaded nanosystems that can release cytotoxic drugs in tumor cells with low off-target effects [ 31 , 32 ]. Despite the several advantages that these innovative therapies may involve, few of them have reached the market.…”