ConspectusCells,特别是活细胞,作为生物活性物质的天然载体。它们固有的低免疫原性和多功能性在疾病治疗应用领域引起了极大的关注。特别是在癌症免疫疗法和再生组织修复领域内。然而,几个突出的挑战阻碍了它们迅速转化为临床应用,包括与大规模生产可行性和高使用成本相关的障碍。为了全面解决这些问题,研究人员提出了通过化学或生物合成手段合成产生的仿生细胞的概念,以模仿细胞功能和行为。然而,人工细胞策略在完全复制活细胞所表现出的复杂功能时遇到困难,同时还要努力解决与临床翻译目的的设计实现相关的复杂性。学科的融合通过一系列方法促进了活细胞的改革,包括化学,生物-,遗传-,和基于材料的方法。这些技术可用于赋予细胞特定功能或增强治疗功效。例如,细胞是通过基因转导来改造的,表面改性,作为递送系统的药物内吞作用,和膜融合。工程细胞的概念为增强对活细胞的控制提供了一个有希望的途径,从而提高治疗效果,同时减轻毒副作用,最终促进精准医疗的实现。在此帐户中,我们全面概述了我们最近在工程细胞领域的研究进展。我们的工作涉及应用生物或化学工程技术来操纵内源性细胞用于治疗或药物递送目的。例如,为了避免艰苦的隔离过程,修改,在体外扩增工程细胞,我们提出了原位工程细胞的概念。通过在神经胶质瘤术后腔内应用装载有携带编辑的嵌合抗原受体(CAR)质粒的纳米颗粒的水凝胶,我们成功地靶向肿瘤相关巨噬细胞进行基因编辑,导致有效的肿瘤复发抑制。此外,利用血小板在损伤部位激活时释放微粒的能力,我们修饰了表面的抗程序性死亡1(PD-1)抗体,以抑制肿瘤术后复发,并为无法手术的肿瘤提供免疫治疗.同样,通过利用细菌对炎症和缺氧部位的积极取向,我们通过工程化细菌提供蛋白质药物,通过启动焦亡和免疫治疗策略诱导癌细胞死亡.在最后一节,我们总结了上述研究进展,同时根据工程细胞的概念,对癌症治疗和临床转化的障碍进行了展望,并提出了潜在的解决方案或未来的方向。
ConspectusCells, particularly living cells, serve as natural carriers of bioactive substances. Their inherent low immunogenicity and multifunctionality have garnered significant attention in the realm of disease treatment applications, specifically within the domains of cancer immunotherapy and regenerative tissue repair. Nevertheless, several prominent challenges impede their swift translation into clinical applications, including obstacles related to large-scale production feasibility and high utilization costs. To address these issues comprehensively, researchers have proposed the notion of bionic cells that are synthetically generated through chemical or biosynthetic means to emulate cellular functions and behaviors. However, artificial cell strategies encounter difficulties in fully replicating the intricate functionalities exhibited by living cells while also grappling with the complexities associated with design implementation for clinical translation purposes. The convergence of disciplines has facilitated the reform of living cells through a range of approaches, including chemical-, biological-, genetic-, and materials-based methods. These techniques can be employed to impart specific functions to cells or enhance the efficacy of therapy. For example, cells are engineered through gene transduction, surface modifications, endocytosis of drugs as delivery systems, and membrane fusion. The concept of engineered cells presents a promising avenue for enhancing control over living cells, thereby enhancing therapeutic efficacy while concurrently mitigating toxic side effects and ultimately facilitating the realization of precision medicine.In this Account, we present a comprehensive overview of our recent research advancements in the field of engineered cells. Our work involves the application of biological or chemical engineering techniques to manipulate endogenous cells for therapeutics or drug delivery purposes. For instance, to avoid the laborious process of isolating, modifying, and expanding engineered cells in vitro, we proposed the concept of in situ engineered cells. By applying a hydrogel loaded with nanoparticles carrying edited chimeric antigen receptor (CAR) plasmids within the postoperative cavity of glioma, we successfully targeted tumor-associated macrophages for gene editing, leading to effective tumor recurrence inhibition. Furthermore, leveraging platelet\'s ability to release microparticles upon activation at injury sites, we modified antiprogrammed death 1 (PD-1) antibodies on their surface to suppress postoperative tumor recurrence and provide immunotherapy for inoperable tumors. Similarly, by exploiting bacteria\'s active tropism toward sites of inflammation and hypoxia, we delivered protein drugs by engineered bacteria to induce cancer cell death through pyroptosis initiation and immunotherapy strategies. In the final section, we summarize our aforementioned research progress while providing an outlook on cancer therapy and the hurdles for clinical translation with potential solutions or future directions based on the concept of engineered cells.