Title : The ultimate trojan horse: Nanocarriers breaking through the bbb for glioblastoma
Abstract:
Glioblastoma (GBM) is the most aggressive form of brain cancer and has a dismal prognosis due to its heterogeneous nature and blood-brain barrier (BBB) issues. The BBB is formed by specialized brain endothelial cells with supporting pericytes and astrocytes, which act as a barrier to therapeutic delivery to the brain, thereby attenuating treatment effectiveness. However, with recent advances in nanotechnology, engineered nanocarriers have emerged that can cross the BBB with efficacy in drug delivery to glioblastoma tumors.
Engineered nanocarriers (nanoparticles and liposomes) can be manufactured to exploit existing mechanisms of entry to the BBB, including receptor-mediated transcytosis (RMT), which utilizes specific receptors on the BBB endothelial cells, such as transferrin receptor 1 (TfR1) and low-density lipoprotein receptor-related protein 1 (LRP1), to translocate large molecules across the barrier. These nanocarriers could be further functionalized with targeting peptides or ligands to bind the abovementioned receptors, considerably enhancing drug accumulation in the brain.
Active strategies also include BBB manipulation methods. Among others, focused ultrasound with microbubbles can obtain a transient opening of BBB, facilitating drug delivery toward the tumor and sparing normal brain tissues to a greater extent. In a further approach, the use of hyperosmolar agents and tight junction modulating agents can improve drug delivery across BBB, though these procedures need to be carefully supervised to prevent undesired effects.
Advances in drug design also provide inputs in the clinical utility of nanocarriers for glioblastoma. Therapeutic agents that are chemically altered may increase lipophilicity and permeability to cells, enabling them to cross the BBB3 with greater efficacy. On the other hand, combination therapies including different drug delivery systems may be beneficial in providing increased efficacy in finding their way through the complex tumor microenvironment of glioblastoma.
In conclusion, engineered nanocarriers expand the promise of overcoming the BBB for glioblastoma drug delivery. By triggering receptor-mediated transcytosis and effecting other BBB-modulation strategies, these systems will improve anticancer drug therapeutic indices and, therefore, could have better treatment outcomes for this challenging disease. Further research needs to optimize carrier design and delivery strategies, making sure for instance safer and more selective delivery to glioblastoma tumors with reduced systemic toxicity.
