title: Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment.
abstract: The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects.
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100191, China.
authors.forename: Binlong
authors.initials: B
authors.lastname: Chen
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Wenbing
authors.initials: W
authors.lastname: Dai
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100191, China.
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100191, China.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100191, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage*; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents
keywords: activatable nanoparticles; drug delivery systems; multistage; stimuli-responsive; tumor microenvironment