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具有黑色素生成的基因设计活细菌,用于肿瘤特异性着色和治疗干预。

Genetically Designed Living Bacteria with Melanogenesis for Tumor-Specific Pigmentation and Therapeutic Intervention.

机构信息

Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, 301 Middle Yanchang Rd., Shanghai, 200072, P. R. China.

Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, 200032, P. R. China.

出版信息

Adv Sci (Weinh). 2024 Aug;11(31):e2402709. doi: 10.1002/advs.202402709. Epub 2024 Jun 18.

DOI:10.1002/advs.202402709
PMID:38889334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11336949/
Abstract

Visual observation and therapeutic intervention against tumors hold significant appeal for tumor treatment, particularly in meeting the demands of intraoperative navigation. From a clinical perspective, the naked-eye visualization of tumors provides a direct and convenient approach to identifying tumors and navigating during surgery. Nevertheless, there is an ongoing need to develop effective solutions in this frontier. Genetically engineered microorganisms are promising as living therapeutics for combatting malignant tumors, leveraging precise tumor targeting and versatile programmed functionalities. Here, genetically modified Escherichia coli (E. coli) MG1655 bacterial cells are introduced, called MelaBac cells, designed to express tyrosinase continuously. This bioengineered melanogenesis produces melanin capable of pigmenting both subcutaneous CT26 xenografts and chemically induced colorectal cancer (CRC). Additionally, MelaBac cells demonstrate the initiation of photonic hyperthermia therapy and immunotherapy against tumors, offering promising selective therapeutic interventions with high biocompatibility.

摘要

肿瘤的可视化观察和治疗干预对肿瘤治疗具有很大的吸引力,特别是在满足术中导航的需求方面。从临床角度来看,肿瘤的肉眼观察为识别肿瘤和手术导航提供了一种直接、便捷的方法。然而,在这一前沿领域仍需要开发有效的解决方案。基因工程微生物作为治疗恶性肿瘤的活体疗法具有很大的应用前景,它们可以利用精确的肿瘤靶向和多功能编程功能。在这里,我们引入了经过基因改造的大肠杆菌(Escherichia coli)MG1655 细菌细胞,称为 MelaBac 细胞,设计为持续表达酪氨酸酶。这种生物工程化的黑色素生成产生了能够使皮下 CT26 异种移植物和化学诱导的结直肠癌(CRC)染色的黑色素。此外,MelaBac 细胞还能够启动光热治疗和肿瘤免疫治疗,为具有高生物相容性的选择性治疗干预提供了有希望的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/a08b46cad76a/ADVS-11-2402709-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/ba4a97180f16/ADVS-11-2402709-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/8241029b9a4b/ADVS-11-2402709-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/e5a088059e40/ADVS-11-2402709-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/65c47443fd18/ADVS-11-2402709-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/ff3b7e81232c/ADVS-11-2402709-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/3d2957224d23/ADVS-11-2402709-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/a08b46cad76a/ADVS-11-2402709-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/ba4a97180f16/ADVS-11-2402709-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/8241029b9a4b/ADVS-11-2402709-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/e5a088059e40/ADVS-11-2402709-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/65c47443fd18/ADVS-11-2402709-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/ff3b7e81232c/ADVS-11-2402709-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/3d2957224d23/ADVS-11-2402709-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ae/11336949/a08b46cad76a/ADVS-11-2402709-g005.jpg

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