Zi-on Cheung

Introduction. Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system, accounting for >60% of all brain tumors in adults while also carrying an extremely poor prognosis of ~12-15 months.¹ As such, more innovative methods are needed in the treatment of GBM, specifically those involving navigating the blood-brain-barrier (BBB) for delivery of therapeutic payloads, such as targeted nanoparticle (NP)-based delivery vehicles coupled with the use of transcytotic transport proteins on the BBB. Consequently, careful investigation of transporter-mediated transcytosis represents a promising avenue for glioblastoma therapy.^2,3 Methods. These studies utilized a range of nanoparticle designs, payload content, and transport protein to explore a variety of methods to navigate the BBB via injection into glioblastoma mice models. One study utilized an anti-OX26 liposome loaded with oxaliplatin within an in vivo mouse model to study the aggregation of both NP and oxaliplatin within brain parenchyma.⁴ Another study leveraged anti-Tf gold nanoparticles without payload to investigate the ability for NPs to transcytose the BBB,⁵ while yet another employed an anti-Tf magnetic dextran-spermine NP system loaded with capecitabine to study the ability to transcytose NPs with an ability to release therapeutic payload.⁶ Results. Liposome-based NP systems were significantly detected within mouse brain parenchyma, indicating its inability to efficaciously transport across the BBB through the OX26 transport protein with its payload. Instead, said liposome-NPs form aggregates along the endothelium of the BBB, and interestingly, while the NPs themselves did not transport across the BBB, their payloads did.⁴ The studies utilizing the Tf receptor involved unloaded gold NPs and a capecitabine-loaded dextran-spermine NP system both demonstrated an ability for the entire nanoparticle system to cross into the brain parenchyma as a whole.^5,6 The dextran-spermine system also demonstrated a marked cytotoxic characterization of its payload.⁶ Conclusions. Studies have demonstrated that the use of trancytotic transport proteins in conjunction with nanoparticle delivery systems shows promise in the development of more effectual treatment of glioblastoma.^4,5,6 Marked increases in either payload and/or nanoparticle system shows the ability to consistently leverage a range of transport proteins within the BBB for pharmaceutical delivery. Additional study may include a more exhaustive exploration of available transport proteins + nanoparticle combinations, biotransport optimization of said combinations, targeted delivered of payloads across the BBB, and the nanoparticle-system clearance across the BBB for systemic removal. ^7,8

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