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Review
. 2025 Jan 18:20:705-721.
doi: 10.2147/IJN.S504629. eCollection 2025.

Design of pH-Responsive Nanomaterials Based on the Tumor Microenvironment

Yunheng Liu #  1 , Longqing Si #  1 , Yuxuan Jiang #  1 , Shaojing Jiang  2 , Xiaokang Zhang  1 , Song Li  1 , Jing Chen  1 , Jinghui Hu  2
Affiliations
Review

Design of pH-Responsive Nanomaterials Based on the Tumor Microenvironment

Yunheng Liu et al. Int J Nanomedicine. .

Abstract

The metabolic activity of tumor cells leads to the acidification of the surrounding microenvironment, which provides new strategies for the application of nanotechnology in cancer therapy. Researchers have developed various types of pH-responsive nanomaterials based on the tumor acidic microenvironment. This review provides an in-depth discussion on the design mechanisms, drug-loading strategies, and application pathways of tumor acidic microenvironment-responsive nanodrug delivery systems. These materials trigger drug release upon reaching the tumor microenvironment, enhancing therapeutic targeting and reducing toxicity to healthy cells. pH-responsive nanomaterials include organic nanomaterials, inorganic nanomaterials, and composite nanomaterials. Additionally, this review outlines the drug-loading strategies, application prospects, and challenges of pH-responsive nanomaterials, aiming to promote the development and clinical translation of this field.

Keywords: drug delivery system; drug-loading strategies; nanocarriers; pH response; tumor microenvironment.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Scheme 1
Scheme 1
Strategies for designing and modifying pH-responsive nanomaterials based on the tumor microenvironment.
Figure 1
Figure 1
The primary molecules involved in pH regulation within cancer cells include: MCT; NHE; AE; CA; NBC; BT; Organelle: V-type ATPase.
See this image and copyright information in PMC

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