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      Targeted Theranostic Nanoparticles for Brain Tumor Treatment

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          Abstract

          The poor prognosis and rapid recurrence of glioblastoma (GB) are associated to its fast-growing process and invasive nature, which make difficult the complete removal of the cancer infiltrated tissues. Additionally, GB heterogeneity within and between patients demands a patient-focused method of treatment. Thus, the implementation of nanotechnology is an attractive approach considering all anatomic issues of GB, since it will potentially improve brain drug distribution, due to the interaction between the blood–brain barrier and nanoparticles (NPs). In recent years, theranostic techniques have also been proposed and regarded as promising. NPs are advantageous for this application, due to their respective size, easy surface modification and versatility to integrate multiple functional components in one system. The design of nanoparticles focused on therapeutic and diagnostic applications has increased exponentially for the treatment of cancer. This dual approach helps to understand the location of the tumor tissue, the biodistribution of nanoparticles, the progress and efficacy of the treatment, and is highly useful for personalized medicine-based therapeutic interventions. To improve theranostic approaches, different active strategies can be used to modulate the surface of the nanotheranostic particle, including surface markers, proteins, drugs or genes, and take advantage of the characteristics of the microenvironment using stimuli responsive triggers. This review focuses on the different strategies to improve the GB treatment, describing some cell surface markers and their ligands, and reports some strategies, and their efficacy, used in the current research.

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          Progress and challenges towards targeted delivery of cancer therapeutics

          Targeted delivery approaches for cancer therapeutics have shown a steep rise over the past few decades. However, compared to the plethora of successful pre-clinical studies, only 15 passively targeted nanocarriers (NCs) have been approved for clinical use and none of the actively targeted NCs have advanced past clinical trials. Herein, we review the principles behind targeted delivery approaches to determine potential reasons for their limited clinical translation and success. We propose criteria and considerations that must be taken into account for the development of novel actively targeted NCs. We also highlight the possible directions for the development of successful tumor targeting strategies.
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            Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications.

            Cancer is a leading cause of death worldwide. Currently available therapies are inadequate and spur demand for improved technologies. Rapid growth in nanotechnology towards the development of nanomedicine products holds great promise to improve therapeutic strategies against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multi-functionality. They can improve the pharmacokinetic and pharmacodynamic profiles of conventional therapeutics and may thus optimize the efficacy of existing anti-cancer compounds. In this review, we discuss state-of-the-art nanoparticles and targeted systems that have been investigated in clinical studies. We emphasize the challenges faced in using nanomedicine products and translating them from a preclinical level to the clinical setting. Additionally, we cover aspects of nanocarrier engineering that may open up new opportunities for nanomedicine products in the clinic.
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              Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

              The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                09 October 2018
                December 2018
                : 10
                : 4
                : 181
                Affiliations
                [1 ]Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; mariamendes1093@ 123456gmail.com (M.M.); jjsousa@ 123456ff.uc.pt (J.J.S.)
                [2 ]Center for Neurosciences and Cell Biology (CNC), University of Coimbra, 3004-504 Coimbra, Portugal
                [3 ]LAQV, REQUIMTE, Group of Pharmaceutical Technology, 3000-548 Coimbra, Portugal
                [4 ]Coimbra Chemistry Centre, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal; pais@ 123456qui.uc.pt
                Author notes
                [* ]Correspondence: csvitorino@ 123456ff.uc.pt ; Tel.: +351-239-487-388
                Article
                pharmaceutics-10-00181
                10.3390/pharmaceutics10040181
                6321593
                30304861
                34dc8ffd-2435-441c-968d-e75976c80efd
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 09 August 2018
                : 27 September 2018
                Categories
                Review

                nanotechnology,glioblastoma,theranostics,gold nanoparticles,lipid nanoparticles,active targeting

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