188宝金博页面版

Asian Journal of Pharmaceutical Sciences 15 (2020) 416–448 Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/AJPS Review Tumor microenvironment responsive drug delivery systems Qunye He a , 1 , Jun Chen a , 1 , Jianhua Yan a , Shundong Cai a , Hongjie Xiong a , Yanfei Liu c , Dongming Peng d , Miao Mo b , ∗ , Zhenbao Liu a , ∗a Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China b Department of Urology, Xiangya Hospital, Central South University, Changsha 410008, China c School of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China d School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China a r t i c l e i n f o Article history: Received 29 April 2019 Revised 30 July 2019 Accepted 21 August 2019 Available online 26 September 2019 Keywords: Cancer therapy Stimuli responsive Dynamic targeting Drug delivery system Controlled release a b s t r a c t Conventional tumor-targeted drug delivery systems (DDSs) face challenges, such as unsatisf i ed systemic circulation, low targeting eff i ciency, poor tumoral penetration, and uncontrolled drug release. Recently, tumor cellular molecules-triggered DDSs have aroused great interests in addressing such dilemmas. With the introduction of several additional functionalities, the properties of these smart DDSs including size, surface charge and ligand exposure can response to different tumor microenvironments for a more eff i cient tumor targeting, and eventually achieve desired drug release for an optimized therapeutic eff i ciency. This review highlights the recent research progresses on smart tumor environment responsive drug delivery systems for targeted drug delivery. Dynamic targeting strategies and functional moieties sensitive to a variety of tumor cellular stimuli, including pH, glutathione, adenosine-triphosphate, reactive oxygen species, enzyme and inf l ammatory factors are summarized. Special emphasis of this review is placed on their responsive mechanisms, drug loading models, drawbacks and merits. Several typical multi-stimuli responsive DDSs are listed. And the main challenges and potential future development are discussed. © 2019 Shenyang Pharmaceutical University. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ) 1. Introduction Tumor microenvironment responsive drug delivery systems are “smart” formulations exhibiting an on-demand drug ∗Corresponding authors. Central South University, No. 172, Tongzipo Road, Changsha 410013, China. Tel.: +86 13723886533. E-mail addresses: docmon@csu.edu.cn (M. Mo), zhenbaoliu@csu.edu.cn (Z.B. Liu). 1 These authors contributed equally to this work. Peer review under responsibility of Shenyang Pharmaceutical University. release prof i le upon response to stimulations from tumor cellular environments, which have aroused great interests in the nano-medical fi eld. Through shrinking or expanding in size, changing of the surface charge, or regulation of https://doi.org/10.1016/j.ajps.2019.08.003 1818-0876/© 2019 Shenyang Pharmaceutical University. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license. ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )