研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

开发自发光生物反应器以增强乳腺癌光动力治疗。

Development of a Self-Luminescent Living Bioreactor for Enhancing Photodynamic Therapy in Breast Cancer.

发表日期:2024 Aug 09
作者: Yanian Xiong, Yingtung Lo, Huizhu Song, Jianzhong Lu
来源: BIOCONJUGATE CHEMISTRY

摘要:

可见光(<2 mm)和近红外(NIR)光(∼1 cm)的穿透能力显着损害光动力疗法(PDT)的治疗效果和临床应用。为了解决光穿透深度的限制,通过将含有荧光素酶基因 teLuc 和亮红色荧光蛋白 mScarlet-I 的融合表达质粒转染到大肠杆菌 Nissle 1917 中,设计了一种新型自发光细菌 teLuc.FP-EcN (ECN)。工程化的 teLuc.FP-EcN 可以特异性地靶向和定植肿瘤,而不会对宿主产生明显的毒性。 teLuc.FP-EcN作为连续的内部光源,可以激活光敏剂二氢卟酚e6(Ce6)产生活性氧(ROS),然后从内部有效破坏肿瘤组织。结果,在小鼠肿瘤模型中观察到肿瘤增殖显着减少,总体生存期延长。此外,teLuc.FP-EcN增强的PDT通过激活抗肿瘤免疫反应来放大其治疗效果,包括将M2巨噬细胞转化为促炎性M1巨噬细胞,以及CD3 T细胞比例的增加和T细胞的减少- 细胞衰竭。总之,teLuc.FP-EcN可作为肿瘤光疗的植入式光源,同时具有ROS生成和免疫调节功能。
The penetration ability of visible light (<2 mm) and near-infrared (NIR) light (∼1 cm) remarkably impairs the therapeutic efficacy and clinical applications of photodynamic therapy (PDT). To address the limitation of light penetration depth, a novel self-luminescent bacterium, teLuc.FP-EcN, has been engineered through transfection of a fusion expression plasmid containing the luciferase gene teLuc and bright red fluorescent protein mScarlet-I into Escherichia coli Nissle 1917 (EcN). The engineered teLuc.FP-EcN can specifically target and colonize tumors without significant toxicity to the host. Acting as a continuous internal light source, teLuc.FP-EcN can activate the photosensitizer chlorin e6 (Ce6) to generate reactive oxygen species (ROS) and then effectively destroy tumor tissue from the inside. As a result, a significant reduction in tumor proliferation and extension of the overall survival in mouse tumor models has been observed. Furthermore, teLuc.FP-EcN-boosted PDT amplified its therapeutic effect by activating antitumor immune response, including the conversion of M2 macrophages into pro-inflammatory M1 macrophages, as well as an increase in the proportion of CD3+ T cells and a decrease in T-cell exhaustion. In conclusion, teLuc.FP-EcN can be used as an implantable light source for tumor phototherapy, which simultaneously possesses ROS generation and immune regulation.