Citation: Haolin Zhang, Kai Feng, Guisen Li, Weijiao Chen, Yuan Shao, Jiayu Ding, Mingming Zheng, Kai Yuan, Xiaolian Sun, Peng Yang. Carbonic anhydrase IX-targeted SMDCs for cancer precision treatment[J]. Chinese Chemical Letters, ;2026, 37(4): 111047. doi: 10.1016/j.cclet.2025.111047 shu

Carbonic anhydrase IX-targeted SMDCs for cancer precision treatment

School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China

xiaolian_sun@cpu.edu.cn

pengyang@cpu.edu.cn

Received Date: 10 December 2024
Revised Date: 3 March 2025
Accepted Date: 6 March 2025
Available Online: 7 March 2025

Figures(4)

In the process of tumor treatment, chemotherapy drugs have been widely used in clinical practice due to their broad-spectrum and significant therapeutic effects. However, the serious side effects caused by off-target effects also limit the actual efficacy of such drugs in clinical. Here, we developed a series of small molecule-drug conjugates (SMDCs) with carbonic anhydrase IX (CAIX)-targeted unit, which can deliver chemotherapy drugs to CAIX-positive cancer cells and release them in the tumor microenvironment. These SMDCs can quickly captured by the highly expressed CAIX on the tumor membrane, forming a high local concentration difference that allows SMDCs to enter the tumor cells faster. The optimized SMDC (CAIXi-R-HCPT) with ROS-sensitive linker showed higher cytotoxicity than Irinotecan. In MDA-MB-231 solid tumor-bearing mice, CAIXi-R-HCPT showed higher tumor/normal tissue (T/N) ratio than the corresponding SMDC and Irinotecan control and it also exhibited in vivo anti-tumor activity comparable to HCPT at the same dosage, and there was no significant weight loss. These findings emphasize the potential of CAIXi-R-HCPT as a promising anti-cancer SMDC that exhibits targeted delivery, tumor-specific release, and strong anti-tumor effects.
- SMDCs,
- Carbonic anhydrase IX,
- Hypoxia,
- Specific response,
- Anti-tumor
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