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Expert Opin Drug Deliv. Author manuscript; available in PMC 2017 February 01. Published in final edited form as: Expert Opin Drug Deliv. 2016 ; 13(3): 311–314. doi:10.1517/17425247.2016.1140147.

ATP-Responsive Drug Delivery Systems Wujin Sun1,2 and Zhen Gu1,2,3,† 1Joint

Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA


of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

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of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC

27599, USA

Keywords ATP responsive; anticancer; drug delivery; DNA aptamer; protein; nanoparticle

1. Introduction

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Advances in material science brought about a wide range of drug delivery systems, from traditional bulk controlled release formulations to modern nanotechnology based carriers, for improved drug efficacy. A wide collection of nanoparticle frameworks, like metallic nanoparticles, liposomes, polymeric nanogels, protein or DNA nanoassemblies, were employed in constructing nanocarriers. Basic nanoparticle framework can be viewed as the chassis of a motor vehicle, upon which various functional modules could be installed, such as targeting ligands for vehicle “steering”, drug binding and environment-sensing moieties for cargo loading and unloading. Uncontrolled drug release from nanocarriers along their way to diseased areas significantly compromises the therapeutic effects while increasing the risk of side effects. The concept of “on-demand” therapeutics would be more promising when the nanocarriers are “smart” to perceive their surrounding environment and react correspondingly. To generate these “smart” formulations for precise delivery, numerous types of stimuli-responsive materials were developed and incorporated into the nanocarriers [1].

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Our group has been devoted to the development of “smart” nanocarriers responsive to a variety of triggers for cancer and diabetes treatment. For example, external physical triggers, like focused ultrasound [2] or tensile strains [3] were applied as hints to control drug dosing. Internal physiological triggers, like overexpressed enzymes (such as furin [4] or hyaluronidase [5]), acidic environment [6], reducing gradients [7], hypoxia [8] or elevated blood glucose levels [9] were also harnessed for controlling drug release. †

Author for correspondence [email protected]. Declaration of interest The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Sun and Gu

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In this editorial, we discuss an emerging strategy utilizing the “molecular unit of currency” in biological energy transfer - ATP - as a trigger for therapeutic delivery. The sharp concentration contrast between extracellular (

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