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Sponsored Artificial Intelligence: A Modern Approach, Global Edition Artificial Intelligence: A Modern Approach, Global Edition

Author

Kang Chen

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Review Open access Aug 2026

Harnessing chitosan-based biomaterials for advanced cancer immunotherapy: from nanocarriers to tumor microenvironment modulation

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. · 0 citations
Open access Jul 2026

Self-assembling pH-responsive peptide nanoparticles delivering pyrvinium pamoate induce osteosarcoma senescence through CBX4 ubiquitination-mediated inhibition of YAP1 SUMOylation.

Osteosarcoma is a highly malignant and metastasis-prone bone tumor, and current treatment options remain unsatisfactory, underscoring the urgent need for new targeted strategies. Induction of cellular senescence represents a promising non-apoptotic antitumor mechanism. Although CK1α is considered to have tumor-suppressive potential, its underlying mechanism and the limited bioavailability of its specific activator pyrvinium pamoate (PP) have hindered clinical translation. Here, we developed a pH-responsive biomineralization-induced peptide self-assembly nanodelivery system (NP@PP) to improve the druggability of PP. Through in vitro and in vivo experiments combined with transcriptomic sequencing, co-immunoprecipitation, and Western blot analysis, we found that PP released from NP@PP efficiently activated CK1α and specifically promoted the ubiquitin-dependent degradation of CBX4. The loss of CBX4 further suppressed YAP1 SUMOylation and blocked its nuclear translocation, thereby activating p16INK4a and p21Cip1 expression, inducing osteosarcoma cell senescence, and inhibiting proliferation and metastasis. In mouse models, NP@PP markedly suppressed xenograft growth and lung metastasis, prolonged survival, and showed no obvious toxicity. These findings reveal a critical role of the CK1α-CBX4-YAP1 signaling axis in senescence-based osteosarcoma therapy and provide a theoretical and practical basis for the development of new nanomedicines.

Renyi Zhou, Yue Ma, Xudong Liu et al. · 0 citations

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