细菌小细胞在癌症治疗中的应用

Role of bacterial minicells in cancer therapy

摘要:

癌症一直是危害人类健康的主要疾病之一。传统的癌症治疗方法包括放疗、化疗和手术，均具有明显的毒副作用或局限性。脂质体和纳米颗粒作为被广泛研究的药物递送载体，在人体临床试验中也出现了药物渗漏和装载功能不全等问题。目前而言，应用具有肿瘤靶向性的载体递送抗肿瘤药物或小分子，是有希望介导安全、有效的肿瘤治疗的策略之一。近年来，细菌来源的非复制型小细胞已受到越来越多的关注。小细胞是细菌异常分裂时期产生的纳米级无核细胞，其直径为200–400 nm，因而具有较大的药物装载能力。对小细胞的表面进行修饰，例如，装配能与肿瘤细胞表面特异性抗原或受体结合的抗体/配体，可显著提高小细胞的肿瘤靶向性。这种具有靶向性的纳米材料能将抗肿瘤的化疗药物、功能性核酸或编码功能性小分子的质粒靶向递送至肿瘤，而减少药物在正常组织器官的集聚。因此，使用小细胞作为靶向递送载体有助于降低药物对机体的毒性，从而最大限度地发挥药物分子在体内的抗肿瘤活性。文中将对小细胞的产生与纯化、药物装载、肿瘤细胞靶向性、内化过程以及其用于递送抗肿瘤药物的研究进展等方面进行综述，为开发基于小细胞的癌症治疗策略提供一定的参考。

Abstract:

Cancer is one of the most important diseases threatening human health. Frequently-used traditional cancer treatment methods, like radiotherapy, chemotherapy and surgery, have serious toxic side effects and limitations. The widely-used drug delivery carriers (liposomes, nanoparticles, etc.) have also possessed many issues such as drug leakage and incomplete loading in the late clinical stage. Currently, using tumor-targeting vectors to deliver anti-tumor drugs or small molecules is one of the promising strategies for mediating safe and effective tumor therapy. In recent years, bacterial-derived non-replicating minicells, which are nanoscale non-nucleated cells produced during abnormal bacterial division, have got more and more attention. With a diameter of 200–400 nm, minicells have a large drug loading capacity. Meanwhile, the surface of minicells are able to be modified to load the assembly of antibodies/ligands that bind to tumor cell surface specific antigens or receptors, which can significantly improve tumor targeting of minicells. This tumor-targeting nanomaterials of minicells not only are used to deliver anti-tumor chemotherapeutic drugs, functional nucleic acids or plasmids encoding functional small molecules to mammalian cells, but also greatly increase drug loading and reduce drug penetration. Thus, the use of minicells combining with chemical therapy could help reduce the toxicity and maximize the effectiveness of the drug in the body. This paper summarizes the research and development of production purification, drug loading, tumor cells targeting, and internalization process of minicells, as well as its use in the delivery of anti-tumor drugs, to provide some information for the development and utilization of minicell carriers.