Lung Cancer Center, Lung Cancer Institute, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, College of Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan 610041, China.
Chin Med J (Engl). 2023 Dec 5;136(23):2787-2801. doi: 10.1097/CM9.0000000000002525.
As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.
作为全球最恶性的肿瘤之一，肺癌由于转移而导致死亡率不断上升。然而，由于其动态的多步骤、复杂和渐进的性质，缺乏有效的临床策略来预防转移。免疫疗法通过逆转肿瘤微环境的免疫抑制网络，在治疗癌症转移方面显示出了希望。然而，由于免疫刺激剂的传递不足和不受控制的免疫反应，不可避免地会产生耐药性。因此，会出现不良反应，如自身免疫，这是由于非靶向器官的非特异性免疫激活和非特异性炎症引起的。纳米载体可以提高药物的溶解度、渗透性、稳定性、生物利用度以及持续、控制和靶向递送，从而有效地克服耐药性，增强治疗效果，同时减少不良反应。特别是，基于纳米医学的免疫疗法可以用于靶向肿瘤转移，为肺癌提供了一种有前途的治疗策略。基于纳米技术的免疫疗法策略是根据与肿瘤免疫微环境相关的转移级联进行分类的；原发性肿瘤的脱离、循环肿瘤细胞的扩散和前转移龛的形成导致远处继发性部位的定植。在这篇综述中，我们专注于将免疫疗法与纳米颗粒制剂相结合，通过调节肿瘤微环境，为临床前和临床应用建立基于纳米技术的免疫疗法，以管理转移性肺癌患者的机会和挑战。我们还讨论了这个新兴领域的前景以及这些技术的临床转化潜力。
