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      Active Cellular and Subcellular Targeting of Nanoparticles for Drug Delivery

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          Abstract

          Nanoparticle (NP)-mediated drug delivery (NMDD) for active targeting of diseases is a primary goal of nanomedicine. NPs have much to offer in overcoming the limitations of traditional drug delivery approaches, including off-target drug toxicity and the need for the administration of repetitive doses. In the last decade, one of the main foci in NMDD has been the realization of NP-mediated drug formulations for active targeted delivery to diseased tissues, with an emphasis on cellular and subcellular targeting. Advances on this front have included the intricate design of targeted NP-drug constructs to navigate through biological barriers, overcome multidrug resistance (MDR), decrease side effects, and improve overall drug efficacy. In this review, we survey advancements in NP-mediated drug targeting over the last five years, highlighting how various NP-drug constructs have been designed to achieve active targeted delivery and improved therapeutic outcomes for critical diseases including cancer, rheumatoid arthritis, and Alzheimer’s disease. We conclude with a survey of the current clinical trial landscape for active targeted NP-drug delivery and how we envision this field will progress in the near future.

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          Analysis of nanoparticle delivery to tumours

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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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              Nanoparticle-based targeted drug delivery.

              Nanotechnology could be defined as the technology that has allowed for the control, manipulation, study, and manufacture of structures and devices in the "nanometer" size range. These nano-sized objects, e.g., "nanoparticles", take on novel properties and functions that differ markedly from those seen from items made of identical materials. The small size, customized surface, improved solubility, and multi-functionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross-disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases such as cancer. This article presents an overview of nanotechnology for the biologist and discusses the attributes of our novel XPclad((c)) nanoparticle formulation that has shown efficacy in treating solid tumors, single dose vaccination, and oral delivery of therapeutic proteins.
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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                18 October 2019
                October 2019
                : 11
                : 10
                : 543
                Affiliations
                Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Code 6900, 4555 Overlook Ave. SW, Washington, DC 20375, USA
                Author notes
                [* ]Correspondence: okhil.nag@ 123456nrl.navy.mil (O.K.N.); james.delehanty@ 123456nrl.navy.mil (J.B.D.); Tel.: +1-202-767-0688 (O.K.N.); +1-202-767-0291 (J.B.D.)
                Author information
                https://orcid.org/0000-0003-3371-1223
                https://orcid.org/0000-0001-9245-3936
                Article
                pharmaceutics-11-00543
                10.3390/pharmaceutics11100543
                6836276
                31635367
                71a699a7-b9ea-4bf0-aa5c-d03495da1508
                © 2019 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
                : 08 September 2019
                : 14 October 2019
                Categories
                Review

                nanoparticles,active targeted drug delivery,cellular,subcellular,organelles,tumor,cancer,rheumatoid arthritis,alzheimer’s disease

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