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. 2023 Jan 3;16(4):5155–5168. doi: 10.1007/s12274-022-5252-z

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

Rizwan Ullah Khan 1, Jinning Shao 1, Jia-Yu Liao 1, Linghui Qian 1,✉
PMCID: PMC9807988  PMID: 36618069

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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Keywords: cancer targeting, pH-responsive, structure-property relationship, charge shifting, acid-labile linkage

Acknowledgements

We acknowledge financial support from the National Natural Science Foundation of China (No. 81903574) and the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China (No. LTZ22B020001). We are also grateful for the financial support from Zhejiang University.

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