Recent advances in application of hydrogel-based nanomaterials in breast cancer: from drug delivery, immunotherapy mechanisms to clinical applications

Abstract Breast cancer remains one of the most prevalent malignant tumors affecting women worldwide and continues posing a major threat to global health. Current clinical treatments include surgery, chemotherapy, radiotherapy, targeted therapy, and endocrine therapy. However, these strategies are frequently limited by challenges such as drug resistance, elevated toxicity, adverse effects, and inadequate modulation of the tumor microenvironment (TME). Recent developments in nanotechnology have enabled the application of nanomaterial-based drug delivery systems that significantly improve delivery efficiency and biocompatibility, reduce drug toxicity and side effects, and demonstrate potential anticancer effects by modulating the TME. Hydrogels, a class of drug carriers, are characterized by a three-dimensional polymer network with high water absorption and retention capacity. Owing to their favorable biocompatibility, degradability, tissue-like physical properties, environmental responsiveness, and functional flexibility, hydrogels have been extensively utilized in biomedical applications, including bone regeneration, wound healing, antibacterial treatments, biosensing, and tumor therapy. Despite these advantages, hydrogels and nanomaterials still confront significant challenges when applied in breast cancer therapy. The integration of functional nanomaterials into the hydrogel matrix can form a novel multifunctional system. This transformation allows hydrogels to serve as targeted delivery platforms for anticancer nanodrugs, enabling synergistic therapeutic effects. This systematic review summarizes recent advances in hydrogel-based nanomaterials for breast cancer therapy, with emphasis on design strategies, mechanisms of action, and immunomodulatory applications. It also critically discusses current limitations and prospects of hydrogel-based nanomaterials. The objective of this review is to help lower interdisciplinary barriers and accelerate the clinical translation of hydrogel-based technologies toward safer, more personalized breast cancer treatments. Graphical Abstract