title: Controllable targeted system based on pH-dependent thermo-responsive nanoparticles.
abstract: In this study, a pH-dependent thermo-responsive polymer (poly (N-isopropyl acrylamide-co-methacrylic acid-co-ethyl methacrylate, P(NIPAAm-co-MAA-co-EMA)), which was used as a masking functional module was designed and prepared. Its LCST was pH-dependent, leading to a sensitive isothermal phase transition between the blood and the extracellular environment of solid tumours. This masking polymer had a LCST of 36.4 °C at pH 6.5, and remained hydrophilic at pH 7.4 even when the temperature was increased to 50 °C. The liver-targeted nanoparticles (NPs) were then obtained by co-grafting the masking functional module and the targeting ligands glycyrrhetinic acid (GA) onto the gold nanoparticles (Au NPs). Their surface properties and targeting ability could be switched based on the expanding or shrinking behaviour of the polymers. The shielding/deshielding effect of GA was confirmed by the bovine serum albumin adsorption and cellular uptake. The results indicated that GA could be shielded by the hydrophilic P(NIPAAm-co-MAA-co-EMA) in the normal physiological environment (pH 7.4, 37 °C) and deshielded in the tumour microenvironment of pH 6.5, 40 °C, leading to an increase in cellular uptake as high as 2.3-fold compared with that observed at pH 7.4, 37 °C. More importantly, the ultrasensitive phase transition of the polymer was reversible, which means that the targeting ability of the deshielded Au NPs could be reshielded if they come back to the blood circulation.
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China.
authors.forename: Chengling
authors.initials: C
authors.lastname: Yang
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China.
authors.forename: Zhenpeng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China. Electronic address: zhiy@nankai.edu.cn.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism*; D053758:Nanoparticles
keywords: Reversible shielding; Thermo-responsive; Tumour targeting; pH-dependent