Beyond nanomicelles and hydrogels: exploring micelle-containing hydrogels as cutting-edge drug delivery system for effective breast cancer treatment.

Breast cancer (BC), the most prevalent global malignancy and second leading cause of mortality in women, presents persistent therapeutic challenges despite various advances in systemic treatments. Additionally, metastasis, recurrence, and chemotherapy-induced toxicities remain significant obstacles. Moreover, the heterogenicity of this disease poses significant challenges for traditional therapies, including poor tumor selectivity, complexity of tumor microenvironment, low solubility of drugs and high toxicity to somatic cells, etc. Targeting the drawbacks of conventional therapies, nano-drug delivery systems, particularly micelles, offer a focused and innovative strategy for cancer treatment. Among these, polymeric micelles and hydrogels have shown substantial potential. Micelles improve drug stability and cellular uptake, whereas hydrogels offer biocompatible, three-dimensional networks for localized and sustained release. The recent studies demonstrate the synergistic interaction of micelle and hydrogel presents a remarkably promising strategy resulting in enhanced drug loading, stability, and tumor-site retention. Moreover, the hybrid micelle-hydrogel composite enables stimuli-responsive, localized delivery within the TME, minimizing systemic toxicity and improving therapeutic outcomes. The hydrogel matrix ensures micellar stability, localized and sustained drug release, while the encapsulated nano micelles enhance drug solubility, stability, and cellular uptake. Consequently, the composite system potentially leads to improved therapeutic efficacy and reduced side effects in a more controlled and targeted manner. The present review delineates the comprehensive details of recent progress in micelle- and hydrogel-based DDS for BC therapy, particularly focusing on the emerging micelle-hydrogel composite platform. Further, the crucial physicochemical properties, biocompatibility and therapeutic performance of the composite system have been critically examined and provide the overview of barriers for their clinical transitions and regulatory consideration. Collectively, the synergistic approach highlights the next generation, multimodal strategy to overcome drawbacks of traditional therapies for the treatment of BC.