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Nano Research

Article Title

pH-sensitive zwitterionic coating of gold nanocages improves tumor targeting and photothermal treatment efficacy

Authors

Ji-Gang Piao, CAS Key Laboratory of Soft Matter Chemistry, and School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China Hangzhou Branch of Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Hangzhou 310018, China
Feng Gao, CAS Key Laboratory of Soft Matter Chemistry, and School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China
Yunong Li, Hefei National Laboratory for Physical Sciences at the Microscale, and School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China
Lei Yu, CAS Key Laboratory of Soft Matter Chemistry, and School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China
Dong Liu, Hefei National Laboratory for Physical Sciences at the Microscale, and School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China
Zi-Bin Tan, CAS Key Laboratory of Soft Matter Chemistry, and School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China
Yujie Xiong, Hefei National Laboratory for Physical Sciences at the Microscale, and School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China
Lihua Yang, CAS Key Laboratory of Soft Matter Chemistry, and School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China
Ye-Zi You, CAS Key Laboratory of Soft Matter Chemistry, and School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China

Keywords

tumor, nanomedicine, photothermal therapy, stealth materials, stimulus-responsive

Abstract

Stealth coating materials effectively extend a nanoparticle’s systemic circulation lifetime yet limit its cellular internalization, which promotes and prevents tumor targeting, respectively. Here, this contradiction was resolved by using an acutely pH-sensitive zwitterionic stealth ligand capable of responding to small differences in extracellular pH between blood and tumors. Using a photothermal gold nanocage (AuNC) as a model nanotherapeutic, we found that stealth-AuNC nanoparticles showed both significantly enhanced cell uptake efficiency in acidic tumors and a markedly extended systemic circulation lifetime compared to its unaltered analogue. As a result, stealth-AuNC nanoparticles administered intravenously showed significantly enhanced accumulation within the tumor, leading to significantly improved photothermal therapeutic efficacy in mouse models. These results suggests that pH-sensitive zwitterionic ligands with sufficient sensitivity for responding to small differences in extracellular pH between blood and tumors are ideal stealth materials for simultaneously conferring both extended systemic circulation and enhanced cellular internalization, reducing the need for active targeting moieties.

Graphical Abstract

Publisher

Tsinghua University Press

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