Nanocarrier-Mediated Immunotherapy for Gynecological Malignancies: Mechanisms, Clinical Translation, and Emerging Nucleic Acid-Based Strategies.

Abstract

Gynecological cancers, including ovarian, cervical, and endometrial cancers, remain major contributors to female morbidity and mortality worldwide. Conventional treatments-surgery, chemotherapy, and radiotherapy-have improved outcomes, but advanced or recurrent disease is still associated with poor prognosis, chemoresistance, and tumor heterogeneity. Immunotherapy has emerged as a transformative strategy because of its specificity and potential for durable responses. However, the immunosuppressive tumor microenvironment and inefficient delivery of immunotherapeutic agents limit clinical benefit. Nanocarriers, including organic, inorganic, and biomimetic platforms, can improve targeted delivery, sustained release, biocompatibility, and tumor microenvironment remodeling, thereby enhancing immunotherapy. This review summarizes major immunotherapeutic modalities for gynecological cancers-immune checkpoint blockade, CAR-T cell therapy, tumor vaccines, and oncolytic viruses-and the classification and characteristics of commonly used nanocarriers. We focus on nanocarrier-mediated immunotherapeutic mechanisms in ovarian, cervical, and endometrial cancers, and further highlight emerging lipid nanoparticle/mRNA and programmable RNA delivery strategies. Finally, we analyze challenges in clinical translation and provide perspectives for future development, aiming to support fundamental research and clinical application of nano-immunotherapy in gynecological malignancies. Gynecological cancers are difficult to treat when they are advanced or come back after treatment. Immunotherapy can help the immune system find and attack cancer cells, but current immunotherapies often do not reach tumors well, and the tumor environment can suppress immune responses. Nanocarriers are tiny delivery systems that can carry immunotherapy drugs to tumors more precisely, protect the drugs from being cleared too quickly, and release them in a controlled way. This review explains how different nanocarriers—such as liposomes, polymeric nanoparticles, inorganic nanoparticles, cell membrane-coated nanoparticles, virus-like particles, and exosomes—can support immunotherapy for ovarian, cervical, and endometrial cancers. We also discuss new approaches such as lipid nanoparticles and mRNA vaccines. These strategies may make immunotherapy safer, more effective, and more personalized. However, more work is needed to improve targeting, reduce long-term toxicity, scale up production, and meet regulatory requirements before these treatments can reach patients.

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