Han Bao, Ning Wang, Xiaowen Zhu, Song Chen, Yang Wang, Xiangjun Han, Hongshan Zhong. Hyaluronic acid-modified polymeric nanoplatform delivering 131I-Hyp suppresses post-ablation residual lesions in colorectal cancer metastases via necrosis-targeted radiotherapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101488
Citation:
Han Bao, Ning Wang, Xiaowen Zhu, Song Chen, Yang Wang, Xiangjun Han, Hongshan Zhong. Hyaluronic acid-modified polymeric nanoplatform delivering 131I-Hyp suppresses post-ablation residual lesions in colorectal cancer metastases via necrosis-targeted radiotherapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101488
Han Bao, Ning Wang, Xiaowen Zhu, Song Chen, Yang Wang, Xiangjun Han, Hongshan Zhong. Hyaluronic acid-modified polymeric nanoplatform delivering 131I-Hyp suppresses post-ablation residual lesions in colorectal cancer metastases via necrosis-targeted radiotherapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101488
Citation:
Han Bao, Ning Wang, Xiaowen Zhu, Song Chen, Yang Wang, Xiangjun Han, Hongshan Zhong. Hyaluronic acid-modified polymeric nanoplatform delivering 131I-Hyp suppresses post-ablation residual lesions in colorectal cancer metastases via necrosis-targeted radiotherapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101488
a. Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang 110001, China;
b. Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, China;
c. Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang 110001, China;
d. Department of Chemistry, School of Forensic Medicine, China Medical University, Shenyang 110122, China
Funds:
This work was supported by the National Natural Science Foundation of China (Grant No.: U21A20378). The authors thank Ruichao Che from the Central Laboratory of the First Hospital of China Medical University for assisting with the fluorescence imaging of the mice. They also thank AJE for English editing.
Despite serving as a radical alternative to surgery for inoperable colorectal hepatic metastases patients, thermal ablation faces local tumor progression rates up to 25% from residual tumors, seriously compromising treatment efficacy and survival of patients. We constructed hyaluronic acid (HA)-modified nanoparticles as carriers for the hydrophobic necrosis-avid agent 131I-hypericin (131I-Hyp), enabling tumor necrosis-targeted radiotherapy. 131I-Hyp was synthesized via iodogen-catalyzed electrophilic substitution and loaded into amphiphilic block copolymer hyaluronan-b-poly(ε-caprolactone) (HA-PCL) using dialysis, yielding HA-PCL@(131I-Hyp) nanoparticles (HP-NPs). HP-NPs were characterized in terms of size, stability, and drug release. Biodistribution and antitumor efficacy in vivo were evaluated in rodent models (nude mice and SRG rats bearing HT-29 subcutaneous tumors) with residual tumors induced by incomplete microwave ablation. HP-NPs showed 84.32% encapsulation efficiency, a uniform spherical shape with a hydrodynamic diameter of 75.66 nm, and rapid cytosolic degradation, enabling the release of 131I-Hyp in necrotic regions. After intravenous injection into animals with residual tumors, HP-NPs accumulated in tumor tissue through the enhanced permeability and retention (EPR) effect and CD44/HA receptor-ligand interactions. The released 131I-Hyp remained selectively in necrotic areas, delivering localized β-radiation to the surrounding residual tumor tissue and significantly inhibiting tumor growth via induction of apoptosis. In conclusion, HP-NPs enable targeted radiotherapy to residual tumor tissue after ablation for colorectal metastases by leveraging necrosis avidity and CD44-mediated HA endocytosis, effectively reducing post-ablation tumor progression. This nanoplatform shows potential for clinical translation in colorectal metastasis treatment.
00305-3e4718fc4-4024-44b6-8474-f6a0707238a8.png)
DownLoad: