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Review Article

pH-triggered cancer-targeting polymers: From extracellular accumulation to intracellular release

Rizwan Ullah KhanJinning ShaoJia-Yu LiaoLinghui Qian( )
Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Cancer Center & Hangzhou Institute of Innovative Medicine, Zhejiang University, Hangzhou 310058, China
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Graphical Abstract

pH-responsive polymers have been developed for cancer-targeting delivery via enhanced cellular entrance due to acidic tumor microenvironment followed by improved release from the endosome/lysosome after endocytosis.

Abstract

Stimuli-responsive polymers are promising to achieve targeted delivery, improved stability during circulation, and controlled release of therapeutic and diagnostic agents. Among them, pH-responsive polymeric nanocarriers have attracted significant attention as pH varies in different body fluids (e.g., stomach, intestine, and colon) and intracellular organelles (e.g., endosome, lysosome, and mitochondria) to maintain homeostasis, while distinctive pH changes are also found in certain pathological states. For example, the extracellular environment of the tumor is acidic, which can be employed to drive selective delivery. During the internalization process, since most nanocarriers enter cells upon endocytosis where a drop of pH from 6.5 to 5.0 can occur from endosome to lysosome, pH-sensitive groups have been developed for enhanced cargo release. In this review, both non-covalent and covalent interactions responsive to pH changes are introduced, with a focus on the structure–property relationship and their applications in cancer targeting and endosomal escape.

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Nano Research
Pages 5155-5168
Cite this article:
Khan RU, Shao J, Liao J-Y, et al. pH-triggered cancer-targeting polymers: From extracellular accumulation to intracellular release. Nano Research, 2023, 16(4): 5155-5168. https://doi.org/10.1007/s12274-022-5252-z
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Received: 17 August 2022
Revised: 23 October 2022
Accepted: 27 October 2022
Published: 03 January 2023
© Tsinghua University Press 2022
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