Fooladi Saba, Rabiee Navid, Iravani Siavash
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06511, USA.
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, WA 6150, Australia.
J Mater Chem B. 2023 Nov 1;11(42):10072-10087. doi: 10.1039/d3tb01805a.
Genetically engineered bacteria (GEB) have shown significant promise to revolutionize modern medicine. These engineered bacteria with unique properties such as enhanced targeting, versatility, biofilm disruption, reduced drug resistance, self-amplification capabilities, and biodegradability represent a highly promising approach for targeted drug delivery and cancer theranostics. This innovative approach involves modifying bacterial strains to function as drug carriers, capable of delivering therapeutic agents directly to specific cells or tissues. Unlike synthetic drug delivery systems, GEB are inherently biodegradable and can be naturally eliminated from the body, reducing potential long-term side effects or complications associated with residual foreign constituents. However, several pivotal challenges such as safety and controllability need to be addressed. Researchers have explored novel tactics to improve their capabilities and overcome existing challenges, including synthetic biology tools (, clustered regularly interspaced short palindromic repeats (CRISPR) and bioinformatics-driven design), microbiome engineering, combination therapies, immune system interaction, and biocontainment strategies. Because of the remarkable advantages and tangible progress in this field, GEB may emerge as vital tools in personalized medicine, providing precise and controlled drug delivery for various diseases (especially cancer). In this context, future directions include the integration of nanotechnology with GEB, the focus on microbiota-targeted therapies, the incorporation of programmable behaviors, the enhancement in immunotherapy treatments, and the discovery of non-medical applications. In this way, careful ethical considerations and regulatory frameworks are necessary for developing GEB-based systems for targeted drug delivery. By addressing safety concerns, ensuring informed consent, promoting equitable access, understanding long-term effects, mitigating dual-use risks, and fostering public engagement, these engineered bacteria can be employed as promising delivery vehicles in bio- and nanomedicine. In this review, recent advances related to the application of GEB in targeted drug delivery and cancer therapy are discussed, covering crucial challenging issues and future perspectives.
基因工程细菌（GEB）已展现出给现代医学带来变革的巨大潜力。这些具有独特特性的工程菌，如增强的靶向性、多功能性、生物膜破坏能力、降低的耐药性、自我扩增能力和生物可降解性，代表了一种极具前景的靶向给药和癌症诊疗方法。这种创新方法涉及对细菌菌株进行改造，使其充当药物载体，能够将治疗剂直接递送至特定细胞或组织。与合成药物递送系统不同，基因工程细菌具有内在的生物可降解性，可自然地从体内清除，从而减少与残留外来成分相关的潜在长期副作用或并发症。然而，仍有一些关键挑战需要解决，如安全性和可控性。研究人员已经探索了新策略来提高其性能并克服现有挑战，包括合成生物学工具（如成簇规律间隔短回文重复序列（CRISPR）和生物信息学驱动的设计）、微生物组工程、联合疗法、免疫系统相互作用和生物遏制策略。由于该领域的显著优势和切实进展，基因工程细菌可能成为个性化医学中的重要工具，为各种疾病（尤其是癌症）提供精确且可控的药物递送。在此背景下，未来的发展方向包括将纳米技术与基因工程细菌相结合、关注针对微生物群的疗法、纳入可编程行为、加强免疫治疗以及发现非医学应用。因此，开发基于基因工程细菌的靶向给药系统需要谨慎的伦理考量和监管框架。通过解决安全问题、确保知情同意、促进公平获取、了解长期影响、减轻两用风险以及促进公众参与，这些工程菌可作为生物医学和纳米医学中很有前景的递送载体。在这篇综述中，讨论了基因工程细菌在靶向给药和癌症治疗应用方面的最新进展，涵盖了关键的挑战性问题和未来展望。
