Xuedong Tang,1,2 Yimin Huang,3 Xiaojuan Zhang,1 Chuanchuan He31College of Medicine, Jiaxing University, Jiaxing, People’s Republic of China; 2Department of Gynaecology, Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children Hospital, Jiaxing University, Jiaxing, People’s Republic of China; 3Department of Central Laboratory, Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children Hospital, Jiaxing University, Jiaxing, People’s Republic of ChinaCorrespondence: Xiaojuan Zhang, College of Medicine, Jiaxing University, Jiaxing, People’s Republic of China, Email xjzhang@zjxu.edu.cn Chuanchuan He, Department of Central Laboratory, Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children Hospital, Jiaxing University, Jiaxing, People’s Republic of China, Email hechuanchuan@zjxu.edu.cnAbstract: Ovarian cancer is one of the most lethal gynecological malignancies. Its immunosuppressive tumor microenvironment and peritoneal dissemination characteristics have severely limited the efficacy of existing immunotherapies. To overcome the poor immunogenicity of tumor antigens and the need for coordinated delivery of antigen and adjuvant, nanovaccines have emerged as a promising strategy. By co-delivering tumor antigens and immunologic adjuvants to antigen-presenting cells, nanovaccines can elicit specific antitumor immune responses. Recently, mRNA-2416, an mRNA-LNP vaccine encoding OX40L, completed a Phase I/II trial in patients with ovarian cancer, providing initial proof-of-concept for intratumoral administration of mRNA-based immunotherapy. This review summarizes antigen design strategies for ovarian cancer nanovaccines and compares the design principles and application progress of major carrier nanoplatforms including liposomes, polymers, inorganic nanoparticles, cell membrane-biomimetic systems, and novel smart responsive nanoplatforms. It further analyzes the core bottlenecks currently facing clinical translation and proposes potential future directions, with the aim of providing a reference for the rational design and clinical translation of ovarian cancer nanovaccines.Keywords: ovarian cancer, nanovaccine, tumor antigen, immune checkpoint inhibitors
Xiaoling Wang,1– 3 Hanlu Chen,1,2 Mei Yang,3 Puwen Chen,1,3 Huapei Kang,1,3 Fangsheng Wang,1– 3 Junyun Huang,1– 3 Tao Ding1– 31Department of Laboratory Medicine, the First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 2College of Medical Technology, Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 3The First School of Clinical Medicine, Gannan Medical University, Ganzhou, 341000, People’s Republic of ChinaCorrespondence: Tao Ding, Email dingtaogmu@163.comAbstract: Extracellular vesicles (EVs) are key mediators of intercellular communication within the tumor microenvironment (TME). In this narrative review, we synthesized relevant studies identified through a systematic search of PubMed and Web of Science (2020– 2026), using search terms including "EVs”, "breast cancer”, "tumor microenvironment”, "biomarkers”, "macrophages”, "fibroblasts”, "T cells”, and "therapy”. Priority was given to peer-reviewed original research and recent high-quality reviews, with study selection based on relevance to EV biology, clinical translation, and methodological rigor. We first outline the potential roles of EVs in breast cancer pathogenesis, including their contribution to an immunosuppressive microenvironment, their regulatory effects on neighboring cells within the TME, and their promotion of malignant phenotypes in epithelial and vascular endothelial cells. Next, we outline studies on EV-based applications for early detection and prognostic stratification. Finally, we introduce emerging EV-related therapeutic strategies—such as adjuvant immunotherapy, stem cell-derived EVs, and engineered EVs—which remain primarily preclinical and face challenges including the lack of standardized isolation and characterization protocols, as well as unresolved issues regarding dosing, safety, and production. EVs are not yet established therapeutic tools; rather, they represent promising but unproven candidate therapies, with most clinical studies focusing on diagnostic applications. Through a narrative and critical review of the relevant literature, this review aims to advance the translation of EV research into more rigorous and practical applications for breast cancer diagnosis and treatment.Keywords: extracellular vesicles, breast cancer, mesenchymal stem cell, tumor microenvironment, macrophages
Lixiang Huang,1,* Yanyan Hu,1,* Yi Yu21Department of Gynecology, Obstetrics and Gynecology Hospital, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 2Hysteroscopy Center, Obstetrics & Gynecology Hospital of Fudan University, Shanghai, 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi Yu, Hysteroscopy Center, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200433, People’s Republic of China, Email icefishyuyi@163.comAbstract: The immunosuppressive post-infection microenvironment (PIM) shaped by persistent human papillomavirus (HPV) infection poses a significant obstacle to the treatment of cervical cancer. In this review, PIM refers to a cervicovaginal local microenvironment initiated and established after HPV infection through complex interactions among HPV-infected keratinocytes, immune cells, host stromal components, and their derivative mediators, including chemokines, cytokines, extracellular vesicles, and metabolites. Ultrasound-responsive nanoplatforms, leveraging their deep penetration and spatiotemporal controllability, can induce immunogenic cell death (ICD) via sonodynamic therapy (SDT) and synergize with targeted delivery and local immune modulation. This review summarizes HPV-driven immune escape, conventional nanomedicine strategies, and ultrasound-responsive platforms for reprogramming PIM in HPV-associated cervical cancer.Keywords: cervical cancer, human papillomavirus, post-infection microenvironment, ultrasound-responsive nanoplatforms, sonodynamic therapy, immunotherapy
Jiayu Xu,1,2 Jiankang Yu,2,3 Gang Liu,2,3 Hao Zhang,2,3 Yue Shen,4,* Jingtong Tang,2,3 Jianping Zhou2,3,*1Department of VIP In-Patient Ward, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Shenyang Medical Nutrition Clinical Medical Research Center, Shenyang, Liaoning, People’s Republic of China; 4Department of Gynecology, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yue Shen, Email 20202166@cmu.edu.cn Jianping Zhou, Email zjphama@163.comBackground: Immune checkpoint inhibitors (ICIs) have transformed the management of mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC), yet the ~95% of patients with mismatch repair-proficient/microsatellite-stable (pMMR/MSS) disease derive little benefit owing to an immunologically "cold” tumor microenvironment (TME), poor T-cell infiltration, myeloid dominance, TGF-β–enriched stroma, and the systemically immunosuppressive milieu imposed by hepatic metastases. Clinically tested combinations—multikinase inhibitor plus anti–PD-1, Fc-enhanced dual checkpoint blockade, chemotherapy– or antiangiogenic–ICI regimens—have so far produced modest, largely non-durable response rates that are further attenuated in liver-metastatic disease, motivating approaches that pharmacologically remodel the TME rather than only release checkpoint restraint.Objective: To provide an evidence-stratified synthesis of nanotechnology-enabled immunotherapy in CRC that explicitly separates (a) clinically established evidence, (b) strategies under early-phase clinical investigation, and (c) concepts that remain preclinical or are extrapolated from other tumor types, and to derive from this appraisal a biomarker-enriched translational research agenda.Methods: Narrative, integrative (non-systematic) review. PubMed, Embase, Web of Science, ClinicalTrials.gov, and ASCO/ESMO/AACR proceedings were searched from January 2010 through April 2026. Each strategy was appraised according to the highest available level of evidence, the tumor type and model system in which the evidence was generated, and its demonstrated CRC specificity.Results: In current clinical practice, nanomedicine in CRC is essentially limited to nanoparticle-formulated cytotoxics exploited for pharmacokinetic advantage (e.g. liposomal irinotecan), whereas nano-enabled immunotherapy is confined to a small number of early-phase trials—most notably lipid nanoparticle (LNP)–formulated individualized neoantigen mRNA vaccines in ctDNA-positive resected CRC and hafnium-oxide nanoparticle radioenhancers—none of which has yet demonstrated a progression-free or overall survival benefit in MSS CRC. Against this background we critically appraise six classes of strategy: (i) LNP-based mRNA neoantigen vaccines; (ii) polymeric and inorganic nanocarriers for STING and TLR agonists; (iii) tumor-associated macrophage–repolarizing nanoparticles; (iv) nano-radiosensitizers and photothermal/photodynamic platforms priming immunogenic cell death; (v) nano-formulated checkpoint inhibitor delivery; and (vi) locoregional nano-strategies directed at hepatic metastasis–specific immunosuppression. For categories (ii)–(vi) the supporting evidence is predominantly murine (largely subcutaneous CT26/MC38 models) or extrapolated from immunologically "hot” tumors such as melanoma and non–small-cell lung cancer, in which both the underlying biology and the checkpoint backbone differ materially from MSS CRC. Recurrent translational barriers include low, highly heterogeneous nanoparticle accumulation in human tumors, dense TGF-β–rich stroma and elevated interstitial pressure, mononuclear phagocyte system clearance, liver-metastasis–specific tolerance that subcutaneous models do not reproduce, unresolved manufacturing/CMC and regulatory pathways, and the absence of validated pharmacodynamic biomarkers of intratumoral immune conversion.Conclusion: Nanotechnology offers a mechanistically coherent and experimentally testable—but at present clinically unproven—set of strategies for converting "cold” MSS CRC into immune-responsive disease. We therefore position nano-enabled immunotherapy as a research priority rather than an imminent standard of care, and argue that its clinical value can only be established through biomarker-enriched, paired-biopsy early-phase trials with pharmacodynamic endpoints of immune conversion and prospective stratification by metastatic site (particularly hepatic involvement) and consensus molecular subtype.Limitations: This is a narrative rather than systematic review; it is therefore subject to selection and publication bias, and much of the evidence synthesized is preclinical and of limited direct translational certainty.Keywords: colorectal cancer, nanomedicine, lipid nanoparticles, immunotherapy, tumor microenvironment, microsatellite stable, immune checkpoint inhibitors, mRNA vaccine, drug delivery
