Chang Xueke, Liu Xiaolin, Wang Xiumei, Ma Lin, Liang Jing, Li Yan
Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Jinan, 250000, People's Republic of China.
Department of Oncology, Yuncheng Chengxin Hospital, Heze, Shandong, 274000, People's Republic of China.
Int J Nanomedicine. 2025 May 7;20:5859-5872. doi: 10.2147/IJN.S516523. eCollection 2025.
Solid tumours possess a hypoxic and immunosuppressive microenvironment, presenting a significant challenge to anticancer treatments. Certain anaerobic microorganisms thrive in this setting, rendering them promising candidates for targeted antitumour therapy delivery. In contrast to traditional nanodrug delivery systems, bacterial-based drug delivery systems can be engineered to produce and secrete therapeutics without the need for intricate post-purification or protective delivery methods. Nevertheless, bacteria can potentially migrate beyond their intended niche, causing off-target drug release and substantial toxicity to healthy tissues. Consequently, to enhance the effectiveness of cancer treatments while minimizing side effects, it is essential to precisely manipulate bacteria for accurate and controlled drug delivery directly to the tumour site. This can be achieved by employing inducible or repressible systems that allow for precise regulation of gene expression at specific times and locations. Ideally, engineering bacteria capable of rapidly and precisely transitioning between "on" and "off" states as required will enable them to recognize and react to targeted stimuli. While various techniques such as optical, magnetic, acoustic, and hyperbaric oxygen micromanipulation have been developed for the manipulation of particles or cells, each technique boasts its unique set of pros and cons. This review article provides an updated overview of the recent progress in the spatiotemporal control of engineered bacteria via these methods and discusses the benefits and constraints of each approach.
实体瘤具有缺氧和免疫抑制的微环境，这给抗癌治疗带来了重大挑战。某些厌氧微生物能在这种环境中茁壮成长，使其成为靶向抗肿瘤治疗递送的有前景的候选者。与传统的纳米药物递送系统不同，基于细菌的药物递送系统可以被设计成产生和分泌治疗剂，而无需复杂的后纯化或保护性递送方法。然而，细菌可能会迁移到预期的生态位之外，导致脱靶药物释放并对健康组织造成严重毒性。因此，为了提高癌症治疗的有效性，同时将副作用降至最低，精确操控细菌以将药物准确、可控地递送至肿瘤部位至关重要。这可以通过采用诱导型或阻遏型系统来实现，该系统允许在特定时间和位置精确调控基因表达。理想情况下，设计出能够根据需要在“开启”和“关闭”状态之间快速精确转换的细菌，将使它们能够识别并对靶向刺激做出反应。虽然已经开发了各种技术，如光学、磁性、声学和高压氧微操控技术来操控颗粒或细胞，但每种技术都有其独特的优缺点。这篇综述文章提供了通过这些方法对工程细菌进行时空控制的最新进展概述，并讨论了每种方法的优点和局限性。
