Next-Generation Hydrogel Platforms for Effective Localized Cancer Therapy: Advances in Biologics, Immunotherapeutics, and Gene Delivery

Despite remarkable advances in nanomedicine, localized delivery of advanced cancer therapeutics remains underexploited. Advanced therapies based on biopharmaceuticals, immunotherapy, or gene therapy have revolutionized oncology. Yet, their systemic administration is often associated with limitations such as poor site-specific accumulation, instability, and systemic toxicity. Hydrogels/macrogels offer the ability to encapsulate, protect, and release biomolecules in situ with sustained and stimulus-responsive profiles, addressing key translational gaps. This review provides a focused synthesis of the last five years of hydrogel-based research for cancer therapy, with emphasis on peptides, antibodies, immunotherapeutic agents, and gene delivery systems. We discuss design principles, release mechanisms, and clinical translation challenges, highlighting structure–function relationships and comparative performance across therapeutic classes. By integrating mechanistic insights with recent breakthroughs, we outline how next-generation hydrogels can synergize with personalized medicine and combination therapies to redefine localized cancer treatment. This work explores the fundamental aspects and provides examples of hydrogel-based delivery for the advanced treatment of cancer. The review summarizes the dynamic landscape of hydrogel research of the last 5 years, showcasing their potential systems for the precise delivery of biomolecules. Specifically, we explore the multidimensional role of hydrogels in the sustained and localized release of antibodies, immunotherapeutic agents, and genes as next-generation platforms for localized cancer treatment. This review aims to critically evaluate the mechanisms and applications of these systems in order to assess their potential to transform medical interventions and advance patient care.