Recent Advances in Spatiotemporal Manipulation of Engineered Bacteria for Precision Cancer Therapy

Xueke Chang,1,* Xiaolin Liu,1,* Xiumei Wang,2,* Lin Ma,1 Jing Liang,1 Yan Li1 1Department 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; 2Department of Oncology, Yuncheng Chengxin Hospital, Heze, Shandong, 274000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Liang, Email [email protected] Yan Li, Email [email protected]: 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. Keywords: engineered bacteria, spatiotemporal manipulation, cancer, light, magnetic, ultrasound, hyperbaric oxygen