What question did this study set out to answer?

To develop a pH-responsive polymeric molecular block for drug-free cancer therapy targeting acidic tumor microenvironments.

February 2, 2026

Concerted pH‐Responsive Performance of Chitosan–Deoxycholic Acid as a Polymeric Molecular Block for Cancer Cell Disruption

Key Points

To develop a pH-responsive polymeric molecular block for drug-free cancer therapy targeting acidic tumor microenvironments.
Synthesis of chitosan succinate-deoxycholic acid nanoparticles
Assessment of particle behavior at varying pH levels
Evaluation of cytotoxicity in cancer and normal cell lines
In vivo tumor suppression studies using mouse models
Significant aggregation of nanoparticles at pH 6.2, preserving smaller size at physiological pH 7.4
Demonstrated selective cytotoxicity against multiple cancer cell lines
Fluorescence imaging showed preferential binding to cancer cells over normal cells
In vivo studies showed significant tumor suppression without conventional drugs

Abstract

Molecular blocks (MBs) offer a drug‐free approach to cancer therapy by utilizing polymeric nanoparticles that remain dispersed in the bloodstream but aggregate within the acidic tumor microenvironment (pH 6.3–6.5) to disrupt cancer cell membranes. Herein, a pH‐responsive polymeric MB is developed by conjugating deoxycholic acid (DCA) to chitosan (CS) through a water‐based modification using CS succinate (CS‐S). The resulting CS‐S–DCA nanoparticles exhibit significant aggregation at pH 6.2 while maintaining a smaller size at physiological pH (7.4), demonstrating pH‐triggered behavior. This leads to selective cytotoxicity against cancer cell lines (MiaPaCa‐2, A‐549, and HT‐29) while preserving compatibility with normal human dermal fibroblasts. Fluorescence imaging confirms preferential adhesion of CS‐S–DCA to cancer cells over normal cells. Encouraged by these findings, in vivo studies in a mouse model are conducted, which reveal significant tumor suppression without the use of conventional drugs. This work highlights the potential of concerted pH‐responsive polymeric MBs as a promising and biocompatible strategy for drug‐free cancer therapy.

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