Immunotherapy has become an important part of the oncotherapy arsenal. Its applicability in various cancer types is impressive, as well as its use of endogenous mechanisms to achieve desired ends. However, off-target or on-target-off-tumor toxicity, limited activity, lack of control in combination treatments and, especially for solid tumors, low local accumulation, have collectively limited clinical use thereof. These limitations are partially alleviated by delivery systems. Lipid-based nanoparticles (NPs) have emerged as revolutionary carriers due to favorable physicochemical characteristics, with specific applications and strengths particularly useful in immunotherapeutic agent delivery. The aim of this review is to highlight the challenges faced by immunotherapy and how lipid-based NPs have been, and may be further utilized to address such challenges. We discuss recent fundamental and clinical applications of NPs in a range of areas and provide a detailed discussion of the main obstacles in immune checkpoint inhibition therapies, adoptive cellular therapies, and cytokine therapies. We highlight how lipid-based nanosystems could address these through either delivery, direct modulation of the immune system, or targeting of the immunosuppressive tumor microenvironment. We explore advanced and emerging liposomal and lipid nanoparticle (LNP) systems for nucleic acid delivery, intrinsic and extrinsic stimulus-responsive formulations, and biomimetic lipid-based nanosystems in immunotherapy. Finally, we discuss the key challenges relating to the clinical use of lipid-based NP immunotherapies, suggesting future research directions for the near term to realize the potential of these innovative lipid-based nanosystems, as they become the crucial steppingstone towards the necessary enhancement of the efficacy of immunotherapy.

中文翻译：

---

基于脂质的纳米系统：下一代癌症免疫疗法


免疫疗法已成为肿瘤治疗库的重要组成部分。它在各种癌症类型的适用性令人印象深刻，以及它利用内源性机制来实现预期目的。然而，脱靶或脱靶肿瘤毒性、有限的活性、联合治疗缺乏控制，尤其是实体瘤的低局部积累，共同限制了其临床使用。交付系统部分缓解了这些限制。由于良好的物理化学特性，基于脂质的纳米颗粒 （NPs） 已成为革命性的载体，其特定应用和强度在免疫治疗剂递送中特别有用。本综述的目的是强调免疫疗法面临的挑战以及基于脂质的 NP 的情况，并可能进一步用于应对这些挑战。我们讨论了 NPs 在一系列领域的最新基础和临床应用，并详细讨论了免疫检查点抑制疗法、过继细胞疗法和细胞因子疗法中的主要障碍。我们重点介绍了基于脂质的纳米系统如何通过递送、直接调节免疫系统或靶向免疫抑制性肿瘤微环境来解决这些问题。我们探索了用于核酸递送的先进和新兴脂质体和脂质纳米颗粒 （LNP） 系统、内源性和外源性刺激响应配方，以及免疫治疗中的仿生脂质纳米系统。 最后，我们讨论了与基于脂质的 NP 免疫疗法的临床应用相关的主要挑战，提出了近期的未来研究方向，以实现这些基于脂质的创新纳米系统的潜力，因为它们成为必要提高免疫疗法疗效的关键垫脚石。