Smart Hydrogel-Nanoparticle Platforms for Precision Drug Delivery and Tumor Microenvironment Modulation in Breast Cancer

Breast cancer accounts for one in four cancers diagnosed in women and remains the leading cause of cancer-related mortality among women worldwide. The drug delivery system (DDS) has created an effective approach in cancer treatment. The current advancement is a combination of nanomaterials with modern nanotechnological strategies, revolutionizing the DDS. Hydrogels provide an exciting route for innovative DDS to deliver various molecules, including peptides, via transdermal, vaginal, nasal, ocular, oral, and other routes. Both natural and synthetic polymeric networks of hydrogels are esteemed for their superior biocompatibility, adjustable mechanical strength, elevated water content, and capacity to encapsulate and release therapeutic agents in a regulated manner, enabling the development of various DDS, including injectable depots, localized implants, and stimuli-responsive formulations designed for specific therapeutic purposes. Hydrogel–nanoparticle systems represent a convergence of material science and cancer biology, offering unprecedented opportunities for pathway-informed drug delivery. Hydrogel-embedded nanoparticle-mediated drug delivery strategies can intentionally shift the balance between survival and death pathways rather than relying on cytotoxicity, with the potential to redefine these systems as programmable therapeutic platforms tailored to the proteomic landscape of breast cancer. Therefore, this review critically discusses how hydrogel–nanoparticle systems offer a promising strategy to modulate the tumor microenvironment by enabling targeted drug delivery, controlled release, enhanced tumor penetration, and improved therapeutic efficacy in breast cancer.