Efficient Therapy of Inflammatory Bowel Disease (IBD) with Highly Specific and Durable Targeted Ta2C Modified with Chondroitin Sulfate (TACS),Advanced Materials

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Efficient Therapy of Inflammatory Bowel Disease (IBD) with Highly Specific and Durable Targeted Ta2C Modified with Chondroitin Sulfate (TACS)
Advanced Materials ( IF 27.4 ) Pub Date : 2023-05-24 , DOI: 10.1002/adma.202301585
Xiangping Song _{1,

2,

3,

4} , Qiong Huang _{3,

5} , Yuqi Yang _{3,

5} , Liang Ma ₆ , Wenguang Liu ₇ , Chunlin Ou ₈ , Qiaohui Chen _{2,

9} , Tianjiao Zhao _{2,

9} , Zuoxiu Xiao _{2,

9} , Mingyuan Wang _{1,

3,

4} , Yitian Jiang _{2,

9} , Yunrong Yang _{3,

5} , Jinping Zhang _{3,

5} , Yayun Nan ₁₀ , Wei Wu _{1,

3,

4} , Kelong Ai _{2,

9,

11}

Affiliation

Department of Geriatric Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410008, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.
Department of General Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China.
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, P. R. China.
Hubei Key Laboratory of Optical Information and Pattern Recognition, Wuhan Institute of Technology, Wuhan, 430205, China.
Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410008, China.
Geriatric Medical Center, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, 750002, China.
Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment., Ministry of Education, Xiangya Hospital, Central South University, Changsha, 410008, China.

Non-invasive localization of lesions and specific targeted therapy are still the main challenges for inflammatory bowel disease (IBD). Ta, as a medical metal element, has been widely used in the treatment of different diseases because of its excellent physicochemical properties but is still far from being explored in IBD. Here, Ta₂C modified with chondroitin sulfate (CS) (TACS) is evaluated as a highly targeted therapy nanomedicine for IBD. Specifically, TACS is modified with dual targeting CS functions due to IBD lesion-specific positive charges and high expression of CD44 receptors. Thanks to the acid stability, sensitive CT imaging function, and strong reactive oxygen species (ROS) elimination ability, oral TACS can accurately locate and delineate IBD lesions through non-invasive CT imaging, and specifically targeted treat IBD effectively because high levels of ROS are a central factor in the progression of IBD. As expected, TACS has much better imaging and therapeutic effects than clinical CT contrast agent and first-line drug 5-aminosalicylic acid, respectively. The mechanism of TACS treatment mainly involves protection of mitochondria, elimination of oxidative stress, inhibiting macrophage M1 polarization, protection of intestinal barrier, and restoration of intestinal flora balance. Collectively, this work provides unprecedented opportunities for oral nanomedicines to targeted therapy of IBD.

中文翻译：

使用硫酸软骨素 (TACS) 修饰的高度特异性和持久的靶向 Ta2C 有效治疗炎症性肠病 (IBD)

无创定位病灶和特异性靶向治疗仍然是炎症性肠病（IBD）的主要挑战。Ta作为一种医用金属元素，因其优异的理化特性而被广泛应用于不同疾病的治疗，但在IBD中的应用还远未得到探索。在此，硫酸软骨素（CS）修饰的Ta _{2 C（TACS）被评估为IBD的高度靶向治疗纳米药物。}具体来说，由于 IBD 病变特异性正电荷和 CD44 受体的高表达，TACS 被修饰为具有双重靶向 CS 功能。凭借其酸稳定性、灵敏的CT成像功能以及强大的活性氧（ROS）消除能力，口服TACS可以通过无创CT成像准确定位和勾画IBD病灶，并针对性地有效治疗IBD，因为高水平的ROS IBD 进展的核心因素。正如预期，TACS 的成像和治疗效果分别比临床 CT 造影剂和一线药物 5-氨基水杨酸好得多。TACS治疗的机制主要涉及保护线粒体、消除氧化应激、抑制巨噬细胞M1极化、保护肠道屏障、恢复肠道菌群平衡等。总的来说，这项工作为口服纳米药物靶向治疗 IBD 提供了前所未有的机会。

更新日期：2023-05-24

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