Department of Chemical and Biological Engineering, Iowa State University, Ames, IA.
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha NE.
Theranostics. 2022 Jan 1;12(3):1030-1060. doi: 10.7150/thno.64805. eCollection 2022.
Pancreatic tumors are highly desmoplastic and immunosuppressive. Delivery and distribution of drugs within pancreatic tumors are compromised due to intrinsic physical and biochemical stresses that lead to increased interstitial fluid pressure, vascular compression, and hypoxia. Immunotherapy-based approaches, including therapeutic vaccines, immune checkpoint inhibition, CAR-T cell therapy, and adoptive T cell therapies, are challenged by an immunosuppressive tumor microenvironment. Together, extensive fibrosis and immunosuppression present major challenges to developing treatments for pancreatic cancer. In this context, nanoparticles have been extensively studied as delivery platforms and adjuvants for cancer and other disease therapies. Recent advances in nanotechnology have led to the development of multiple nanocarrier-based formulations that not only improve drug delivery but also enhance immunotherapy-based approaches for pancreatic cancer. This review discusses and critically analyzes the novel nanoscale strategies that have been used for drug delivery and immunomodulation to improve treatment efficacy, including newly emerging immunotherapy-based approaches. This review also presents important perspectives on future research directions that will guide the rational design of novel and robust nanoscale platforms to treat pancreatic tumors, particularly with respect to targeted therapies and immunotherapies. These insights will inform the next generation of clinical treatments to help patients manage this debilitating disease and enhance survival rates.
胰腺肿瘤具有高度促结缔组织增生和免疫抑制特性。由于内在的物理和生化压力导致间质液压力增加、血管受压和缺氧，药物在胰腺肿瘤内的输送和分布受到影响。基于免疫疗法的方法，包括治疗性疫苗、免疫检查点抑制、CAR-T 细胞疗法和过继性 T 细胞疗法，受到免疫抑制肿瘤微环境的挑战。广泛的纤维化和免疫抑制共同给开发胰腺癌治疗方法带来了重大挑战。在这种情况下，纳米颗粒作为癌症和其他疾病治疗的药物输送平台和佐剂得到了广泛研究。纳米技术的最新进展导致了多种基于纳米载体的制剂的开发，这些制剂不仅改善了药物输送，还增强了针对胰腺癌的免疫疗法。本文讨论并批判性地分析了用于药物输送和免疫调节以提高治疗效果的新型纳米级策略，包括新出现的免疫疗法。本文还对未来的研究方向提出了重要的观点，这些观点将指导新型和强大的纳米级平台的合理设计，以治疗胰腺肿瘤，特别是针对靶向治疗和免疫治疗。这些见解将为下一代临床治疗提供信息，帮助患者应对这种衰弱性疾病并提高生存率。
