Injectable hydrogel-based platforms for precision lung cancer therapy: bridging biomaterials and oncology

Lung cancer is the leading cause of cancer-related deaths globally, with around 2.5 million new cases and 1.8 million fatalities reported each year, driven by late-stage diagnosis, aggressive tumor biology, and limited efficacy of systemic therapies due to poor tumor penetration and dose-limiting toxicities. These clinical challenges underscore the urgent need for localized, precision drug delivery strategies. This review critically examines injectable hydrogel-based platforms as emerging solutions for precision lung cancer therapy, focusing on their design principles, therapeutic mechanisms, and translational potential. Recent literature highlights three transformative advances: (i) in situ-forming hydrogel depots that enable sustained intratumoral drug retention while minimizing systemic exposure; (ii) multifunctional hydrogels capable of co-delivering chemotherapeutics, immunomodulators, or phototherapeutic agents to synergistically remodel the tumor microenvironment; and (iii) stimuli-responsive systems that exploit tumor-specific cues (pH, enzymes, redox state) to achieve on-demand drug release and enhanced therapeutic precision. Preclinical studies consistently demonstrate improved antitumor efficacy, reduced off-target toxicity, and compatibility with radiotherapy, photothermal therapy, and immune checkpoint blockade. Despite these advances, clinical translation remains constrained by key hurdles, including scalable manufacturing, sterilization, long-term biocompatibility, and regulatory standardization. Addressing these challenges will be critical to advancing injectable hydrogels from promising experimental platforms to clinically deployable therapies for lung cancer.