Tailored nanocarriers and bioconjugates for combating glioblastoma and other brain tumors

Abstract

Worldwide, the incidence of primary brain tumors is on the rise. Unfortunately, noninvasive drug therapy is hampered by poor access of most drugs to the brain due to the insurmountable blood-brain barrier (BBB). Nanotechnology holds great promise for noninvasive therapy of severe brain diseases. Furthermore, recent bioconjugation strategies have enabled the invasion of the BBB via tailored-designed bioconjugates either with targeting moieties or alterations in the physicochemical and/or the pharmacokinetic parameters of central nervous system (CNS) active pharmaceutical ingredients. Multifunctional systems and new entities are being developed to target brain cells and tumor cells to resist the progression of brain tumors. Direct conjugation of an FDA-approved drug with a targeting moiety, diagnostic moiety, or pharmacokinetic-modifying moiety represents another current approach in combating brain tumors and metastases. Finally, genetic engineering, stem cells, and vaccinations are innovative nontraditional approaches described in different patents for the management of brain tumors and metastases. This review summarizes the recent technologies and patent applications in the past five years for the noninvasive treatment of glioblastoma and other brain tumors. Till now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are ongoing to bring novel CNS delivery systems to potential clinical application.

Development of Polymer-Based Nanoformulations for Glioblastoma Brain Cancer Therapy and Diagnosis: An Update

“…BBB is compromised in human glioma cells because of the leaky inter endothelial tight junction and poorly differentiated astrocytes that are unable to release essential components for BBB function [31,36]. In this case, it is termed as blood-brain tumour barrier (BBTB) or blood-tumour barrier (BTB) [14] (Figure 1). In low-grade gliomas, the structure and function of the BBTB resemble normal BBB, while in hi-grade glioma, BBB is significantly altered, disrupted.…”

“…Glial cell originated gliomas include glioblastomas, astrocytomas, schwannomas, oligodendrogliomas, etc. [ 14 ]. According to World Health Organization (WHO), glioma tumours of CNS is classified into four grades based on aggressiveness, Grade I pilocytic astrocytoma, Grade II diffuse astrocytoma, Grade III anaplastic astrocytoma, and Grade IV glioblastoma [ 12 ].…”

Overcoming the blood–brain barrier in neurodegenerative disorders and brain tumours

“…Because of small size, easy manipulation of structure and properties, active carrying and controlled release of therapeutic agents, in recent years nanoparticles (NPs) take increased attention from scientists [105, 106]. NPs are 1 to 1000 nm colloidal carriers that can be produced as synthetic or natural.…”

Is active targeting of brain metastases of breast cancer superior to passive targeting?

“…Although, there are no FDA-approved systemic treatments for BCBM to date [41] , patents and studies in the past years have shown promising progress and well-established techniques to overcome the BBB/ BBTB [42] . There are two general strategies adopted to facilitate crossing the BBB; invasive and non-invasive techniques [43] .…”