Cancer immunotherapy has transformed oncology, however, its clinical efficacy remains limited by immunosuppressive tumor microenvironments (TMEs), poor therapeutic delivery, systematic toxicity, treatment resistance. Chitosan, a biocompatible and biodegradable polysaccharide, has emerged as a versatile biomaterial capable of addressing these challenges through both intrinsics immunomodulatory activity and advanced drug-delivery functions. This review summarizs recent advances in chitosan-based biomaterials for cancer immunotherapy, highlighting their ability to activate innate and adaptive immune responses through pathways involving patterns recognition receptors, cyclic GMP-AMP synthase (cGAS)=simulator of interferon genes (STING) signaling, dendric cells (DCs)macrophages, natural killer (NK) cells and T lymphocytes. The design and application of chitosan-based nanoparticles and hydrogels as platformsfor delivering cytokines, nucleic acids, immune adjuvant, cancer vaccines and immune checkpoint therapeutics are discussed. Particular attention is given to their roles in TME remodeling, sustained local drug release, postsurgical immunotherapy, and combination approaches that integrate chemotherapy, radiotherapy (RT), phototherapy and immunotherapy. Emerging strategies, including stimuli-responsive systems, biomimetic formulations, and multifunctional nanoplatforms are also discussed. Finally, we discuss the current translational current translational challenges and future perspectives, emphasizing the potential of chitosan-based biomaterials to enhance antitumor immunity and improve clinical outcomes in cancer immunotherapy. Chitosan biomaterials enhance antitumor immunity through intrinsic immunomodulatory activity. Chitosan nanoparticles and hydrogels enable efficient delivery of immunotherapeutic agents. Chitosan-based systems remodel the tumor microenvironment and promote immune activation. Combination therapies that integrate chitosan platforms improve therapeutic efficacy and reduce toxicity. Stimuli-responsive and multifunctional chitosan nanoplatforms offer promising strategies for precision cancer immunotherapy.
Yun Wang, Yan Fan, Jing Zhang et al.· Journal of Nanobiotechnology· 0 citations
Cancer immunotherapy has substantially advanced cancer treatment; however, durable responses remain uncommon in tumors with low immunogenicity and strongly suppressive tumor microenvironments (TME). Among innate immune pathways, cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling has attracted considerable attention because of its ability to initiate broad antitumor immune responses. Despite this promise, the therapeutic use of STING agonists is limited by rapid systemic clearance, insufficient tumor accumulation, and dose-limiting inflammatory toxicity. Simultaneously, metabolic adaptations within tumors, including elevated glycolytic flux, lactate enrichment, and redox imbalance, continue to undermine immune cell function and restrict treatment efficacy. Zn-based nanoplatforms have recently emerged as versatile systems capable of simultaneously addressing both challenges. Controlled intracellular release of Zn2+ can potentiate cGAS activity and strengthen downstream STING signaling, whereas oxidative stress induced by these nanomaterials promotes DNA damage, cytosolic DNA leakage, and immunogenic cell death. These effects are not limited to the activation of innate immunity. Several Zn-containing nanoplatforms reshape the metabolic landscape of the TME by lowering lactate accumulation and partially restoring immune cell activity. Consequently, dendritic cell (DC) maturation and antigen presentation are enhanced, leading to more effective T cell-driven antitumor responses. This review examines the emerging role of Zn2+ in regulating the immune and metabolic pathways relevant to cancer therapy. We discuss current strategies for designing Zn-based nanoplatforms, with particular emphasis on the mechanisms linking metabolic intervention to cGAS-STING activation. Dedicated sections examine Zn-based platforms for drug delivery and photodynamic and sonodynamic therapies, as well as their capacity to promote DC activation and combination immunotherapy. Finally, we consider the major barriers to clinical translation, including biosafety, delivery efficiency, and large-scale manufacturing, and outline the directions for the development of next-generation Zn-based immunotherapeutic systems. STATEMENT OF SIGNIFICANCE: This review provides a comprehensive, mechanistically integrated perspective on Zn-based nanoplatforms as multifunctional immunotherapeutic systems that bridge tumor metabolic reprogramming and cGAS-STING-mediated innate and adaptive immune activation. Unlike previous reviews that primarily focused on STING agonists or Zn-based nanomaterials independently, this study highlights how tumor-responsive Zn²⁺ release, oxidative stress, DNA damage, and metabolic remodeling collectively enhance antitumor immunity. This review critically compares the design principles, therapeutic mechanisms, and translational potential of diverse Zn-based nanoplatforms and discusses the key challenges in biosafety, manufacturing, and clinical translation. This review offers a conceptual framework to guide the rational development of next-generation Zn-based nanomedicines for precision cancer immunotherapy.
Its complex interactome, which includes cytoskeletal regulators, molecular chaperones, nuclear transport proteins, and cell surface receptors, positioning S100A6 as a central signaling hub, is detailed.
Jing Zhang, Peng Tang, Linshu Huang et al.· Frontiers in Pharmacology· 0 citations
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