By Gerardo Caruso, M.D., Maria Caffo Ph.D, M.D., Giuseppe Raudino, M.D., and Francesco Tomasello, M.D.
Biomedical & Nanomedical Technologies (B&NT): Concise Monographs Series
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Up to 40 volumes are planned for this concise monograph series, which focuses on the implementation of various engineering principles in the conception, design, development, analysis and operation of biomedical, biotechnological and nanotechnology systems and applications.
Abstract: Despite progress in surgery, radiotherapy, and in chemotherapy, an effective curative treatment of gliomas does not yet exist. Mortality is still close to 100% and the average survival of patients with GBM is less than 1 year. The efficacy of current anti-cancer strategies in brain tumors is limited by the lack of specific therapies against malignant cells. Besides, the delivery of the drugs to brain tumors is limited by the presence of the blood brain barrier. The oncogenesis of gliomas is characterized by several biological processes and genetic alterations, involved in the neoplastic transformation. The modulation of gene expression to more levels, such as DNA, mRNA, proteins and transduction signal pathways, may be the most effective modality to down-regulate or silence some specific gene functions. Gliomas are characterized by extensive microvascular proliferation and a higher degree of vasculature. In malignant gliomas targeted therapies efficacy is low.
In this complex field, it seems to be very important to improve specific selective drugs delivery systems. Drugs, antisense oligonucleotides, small interference RNAs, engineered monoclonal antibodies and other therapeutic molecules may diffuse into CNS overcoming the BBB. Nanotechnology could be used both to improve the treatment efficacy and to reduce the adverse side effects. Nanotechnology-based approaches to targeted delivery of drugs across the BBB may potentially be engineered to carry out specific functions as needed. Moreover, nanoparticles show tumor-specific targeting and long blood circulation time, with consequent low-short-term toxicity. Nanotechnology deals with structures and devices that are emerging as a new field of research at the interface of science, engineering and medicine. Nanomedicine, the application of nanotechnology to healthcare, holds great promise for revolutionizing medical treatments, imaging, faster diagnosis, drug delivery and tissue regeneration.
This technology has enabled the development of nanoscale device that can be conjugated with several functional molecules including tumor-specific ligands, antibodies, anticancer drugs, and imaging probes. Nanoparticle systems are, also emerging as potential vectors for brain delivery, able to overcome the difficulties of the classical strategies. By using nanotechnology it is possible to deliver the drug to the targeted tissue across the BBB, release the drug at the controlled rate, and avoid from degradation processes. At the same time, it is also necessary to retain the drug stability and ensure that early degradation of drugs from the nanocarriers does not take place. Large amounts of small molecules, such as contrast agents or drugs, can be loaded into NPs via a variety of chemical methods including encapsulation, adsorption, and covalent linkage.
Most targeting molecules can be added to the surface of NPs to improve targeting through a concept defined as surface-mediated multivalent affinity effects. The future challenges may be the possibility to modify the cell genome and induce it to a reversion to the wild-type conditions and the enhancing of immune system anti-tumor capacity. Recent advances in molecular, biological and genetic diagnostic techniques have begun to explore cerebral glioma-associated biomarkers and their implications for gliomas development and progression. Realization of targeted therapies depends on expression of the targeted molecules, which can also provide as specific biomarkers. The development of multifunctional NPs may contribute to the achievement of targeted therapy in glioma treatment.
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