Reversibly Extracellular pH Controlled Cellular Uptake and Photothermal Therapy by PEGylated Mixed‐Charge Gold Nanostars |
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| Authors: | Shouju Wang Zhaogang Teng Peng Huang Dingbin Liu Ying Liu Ying Tian Jing Sun Yanjun Li Huangxian Ju Xiaoyuan Chen Guangming Lu |
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| Affiliation: | 1. Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, P.R. China;2. State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, P.R. China;3. Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, USA;4. State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center of Chemical Science and Engineering, and Research Center for Analytical Sciences, College of Chemistry, Nankai University, Tianjin, P.R. China |
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| Abstract: | Shielding nanoparticles from nonspecific interactions with normal cells/tissues before they reach and after they leave tumors is crucial for the selective delivery of NPs into tumor cells. By utilizing the reversible protonation of weak electrolytic groups to pH changes, long‐chain amine/carboxyl‐terminated polyethylene glycol (PEG) decorated gold nanostars (GNSs) are designed, exhibiting reversible, significant, and sensitive response in cell affinity and therapeutic efficacy to the extracellular pH (pHe) gradient between normal tissues and tumors. This smart nanosystem shows good dispersity and unimpaired photothermal efficacy in complex bioenvironment at pH 6.4 and 7.4 even when their surface charge is neutral. One PEGylated mixed‐charge GNSs with certain surface composition, GNS‐N/C 4 , exhibits high cell affinity and therapeutic efficacy at pH 6.4, and low affinity and almost “zero” damage to cells at pH 7.4. Remarkably, this significant and sensitive response in cell affinity and therapeutic efficacy is reversible as local pH alternated. In vivo, GNS‐N/C 4 shows higher accumulation in tumors and improved photothermal therapeutic efficacy than pH‐insensitive GNSs. This newly developed smart nanosystem, whose cell affinity reversibly transforms in response to pHe gradient with unimpaired biostability, provides a novel effective means of tumor‐selective therapy. |
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| Keywords: | controllable cellular uptake PEGylated mixed‐charge nanoparticles photothermal therapy reversibly pH responsive tumor‐targeted delivery |
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