State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy & Chongqing Key Laboratory of Soft-Matter Material Chemistry and Function Manufacturing, Southwest University, Chongqing 400715, China.
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
Chem Soc Rev. 2022 Jun 20;51(12):5136-5174. doi: 10.1039/d2cs00247g.
Recent years have witnessed increasingly rapid advances in nanocarrier-based biomedicine aimed at improving treatment paradigms for cancer. Nanogels serve as multipurpose and constructed vectors formed intramolecular cross-linking to generate drug delivery systems, which is attributed predominantly to their satisfactory biocompatibility, bio-responsiveness, high stability, and low toxicity. Recently, immunotherapy has experienced unprecedented growth and has become the preferred strategy for cancer treatment, and mainly involves the mobilisation of the immune system and an enhanced anti-tumour immunity of the tumour microenvironment. Despite the inspiring success, immunotherapeutic strategies are limited due to the low response rates and immune-related adverse events. Like other nanomedicines, nanogels are comparably limited by lower focal enrichment rates upon introduction into the organism injection. Because nanogels are three-dimensional cross-linked aqueous materials that exhibit similar properties to natural tissues and are structurally stable, they can comfortably cope with shear forces and serum proteins in the bloodstream, and the longer circulation life increases the chance of nanogel accumulation in the tumour, conferring deep tumour penetration. The large specific surface area can reduce or eliminate off-target effects by introducing stimuli-responsive functional groups, allowing multiple physical and chemical modifications for specific purposes to improve targeting to specific immune cell subpopulations or immune organs, increasing the bioavailability of the drug, and conferring a low immune-related adverse events on nanogel therapies. The slow release upon reaching the tumour site facilitates long-term awakening of the host's immune system, ultimately achieving enhanced therapeutic effects. As an effective candidate for cancer immunotherapy, nanogel-based immunotherapy has been widely used. In this review, we mainly summarize the recent advances of nanogel-based immunotherapy to deliver immunomodulatory small molecule drugs, antibodies, genes and cytokines, to target antigen presenting cells, form cancer vaccines, and enable chimeric antigen receptor (CAR)-T cell therapy. Future challenges as well as expected and feasible prospects for clinical treatment are also highlighted.
近年来，基于纳米载体的生物医学取得了飞速发展，旨在改善癌症的治疗模式。纳米凝胶作为多功能构建载体，通过分子内交联形成，是药物传递系统的主要组成部分，这主要归因于其令人满意的生物相容性、生物响应性、高稳定性和低毒性。近年来，免疫疗法经历了前所未有的发展，已成为癌症治疗的首选策略，主要涉及免疫系统的动员和增强肿瘤微环境的抗肿瘤免疫力。尽管取得了令人鼓舞的成功，但免疫治疗策略受到限制，因为响应率低和免疫相关的不良反应。与其他纳米药物一样，纳米凝胶在引入生物体时的局部富集率也相对较低。由于纳米凝胶是三维交联的水性材料，具有与天然组织相似的性质，结构稳定，因此可以轻松应对血流中的剪切力和血清蛋白，更长的循环寿命增加了纳米凝胶在肿瘤中积累的机会，赋予其更深的肿瘤穿透性。较大的比表面积可以通过引入响应性功能基团来减少或消除脱靶效应，允许进行多种物理和化学修饰以达到特定目的，从而提高对特定免疫细胞亚群或免疫器官的靶向性，提高药物的生物利用度，并降低纳米凝胶治疗的免疫相关不良反应。到达肿瘤部位后的缓慢释放有利于宿主免疫系统的长期唤醒，最终实现增强的治疗效果。作为癌症免疫治疗的有效候选物，基于纳米凝胶的免疫疗法得到了广泛应用。在这篇综述中，我们主要总结了基于纳米凝胶的免疫疗法在递送免疫调节小分子药物、抗体、基因和细胞因子方面的最新进展，以靶向抗原呈递细胞、形成癌症疫苗，并实现嵌合抗原受体（CAR）-T 细胞治疗。还强调了未来的挑战以及对临床治疗的预期和可行前景。
