title: Responsive Nanocarriers as an Emerging Platform for Cascaded Delivery of Nucleic Acids to Cancer.
abstract: Cascades of systemic and intracellular obstacles, including low stability in blood, little tumor accumulation, weak tumor penetration, poor cellular uptake, inefficient endosomal escape and deficient disassembly in the cytoplasm, must be overcome in order to deliver nucleic acid drugs for cancer therapy. Nanocarriers that are sensitive to a variety of physiological stimuli, such as pH, redox status, and cell enzymes, are substantially changing the landscape of nucleic acid drug delivery by helping to overcome cascaded systemic and intracellular barriers. This review discusses nucleic acid-based therapeutics, systemic and intracellular barriers to efficient nucleic acid delivery, and nanocarriers responsive to extracellular and intracellular biological stimuli to overcome individual barriers. In particular, responsive nanocarriers for the cascaded delivery of nucleic acids in vivo are highlighted. Developing novel cascaded nanocarriers that transform their physicochemical properties in response to various stimuli in a timely and spatially controlled manner for nucleic acid drug delivery holds great potential for translating the promise of nucleic acid drugs and achieving clinically successful cancer therapy.
authors.affiliation: School of Life Sciences, University of Science & Technology of China, Hefei, Anhui, 230027, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, 510006, P.R. China.
authors.forename: Cong-Fei
authors.initials: CF
authors.lastname: Xu
authors.affiliation: School of Life Sciences, University of Science & Technology of China, Hefei, Anhui, 230027, P.R. China.
authors.forename: Shoaib
authors.initials: S
authors.lastname: Iqbal
authors.affiliation: Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, 510006, P.R. China. Electronic address: yangxz@hfut.edu.cn.
authors.forename: Xian-Zhu
authors.initials: XZ
authors.lastname: Yang
authors.affiliation: Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, 510006, P.R. China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou, Guangdong, 510006, P.R. China. Electronic address: mcjwang@scut.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy*; D009696:Nucleic Acids / Q000008:administration & dosage*
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D009696:Nucleic Acids
keywords: cascaded delivery; multiple barriers; nucleic acid; responsive nanocarriers; tumor microenvironment