Abstract
The acidic tumor microenvironment (pH 6.3–6.8) provides a powerful endogenous trigger for targeted nanomedicine. Acid-triggered self-assembling polymeric nanoparticles leverage pH-responsive chemical bonds and ionizable polymers to undergo structural transformations selectively within tumors. This enables controlled drug release, improved cellular uptake, and targeted hypoxia therapy. Recent innovations integrate these pH-sensitive platforms with hypoxia-responsive moieties, oxygen generation, photodynamic therapy, immunotherapy, gene delivery, and imaging capabilities. This review highlights molecular design strategies, self-assembly mechanisms, and multifunctional nanoplatforms while evaluating current preclinical progress, clinical translation challenges, and future perspectives for precision cancer therapy.
