title: Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies.
abstract: Despite recent technological advancements and promising preclinical experiments, brain tumor patients are still met with limited treatment options. Some of the barriers to clinical improvements include the systemic toxicity of cytotoxic compounds, the impedance of the blood brain barrier (BBB), and the lack of therapeutic agents that can selectively target the intracranial tumor environment. To overcome such barriers, a number of chemotherapeutic agents and nucleic acid-based therapies are rapidly being synthesized and tested as new brain tumor-targeted delivery strategies. Novel carriers include liposomal and polymeric nanoparticles, wafers, microchips, microparticle-based nanoplatforms and cells-based vectors. Strong preclinical results suggest that these nanotechnologies are set to transform the therapeutic paradigm for brain tumor treatment. In addition to new tumoricidal agents, parallel work is also being conducted on the BBB front. Preclinical testing of chemical and physical modulation strategies is yielding improved intracranial concentrations. New diagnostic and therapeutic imaging techniques, such as high-intensity focused ultrasound and MRI-guided focused ultrasound, are being used to modulate the BBB in a more precise and non-invasive manner. This review details some of the tremendous advances that are being explored in current brain tumor targeted therapies, including local implant development, nanobiotechnology-based delivery strategies, and techniques of BBB manipulation.
authors.affiliation: Koch Cancer Research Building, 1550 Orleans Street, Baltimore, MD, 21231, USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Mangraviti
authors.affiliation: Koch Cancer Research Building, 1550 Orleans Street, Baltimore, MD, 21231, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gullotti
authors.affiliation: Koch Cancer Research Building, 1550 Orleans Street, Baltimore, MD, 21231, USA. Electronic address: btyler@jhmi.edu.
authors.forename: Betty
authors.initials: B
authors.lastname: Tyler
authors.affiliation: Koch Cancer Research Building, 1550 Orleans Street, Baltimore, MD, 21231, USA.
authors.forename: Henry
authors.initials: H
authors.lastname: Brem
mesh_terms: D000818:Animals; D001709:Biotechnology / Q000379:methods*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008081:Liposomes; D058990:Molecular Targeted Therapy / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D010539:Permeability; D000069453:Ultrasonic Waves
chemical_list: D004337:Drug Carriers; D008081:Liposomes
keywords: BBB permeability; Focused ultrasound; High-intensity; High-intensity focused ultrasound; Local delivery; Nanostrategies