C-C趋化因子受体7型
癌症研究
转移
CCL21型
淋巴
淋巴系统
原发性肿瘤
趋化因子受体
趋化因子
医学
化学
癌症
免疫学
免疫系统
病理
内科学
作者
Yueyang Deng,Changyin Tan,Shuguang Huang,Honghao Sun,Zhaoting Li,Jing Li,Zhanwei Zhou,Minjie Sun
标识
DOI:10.1002/adhm.202201166
摘要
Abstract Tumor metastasis contributes to high cancer mortality. Tumor cells in lymph nodes (LNs) are difficult to eliminate but underlie uncontrollable systemic metastasis. The CC chemokine receptor 7 (CCR7) is overexpressed in tumor cells and interacts with CC chemokine ligand 21 (CCL21) secreted from LNs, potentiating their lymphatic migration. Here, a site‐specific polyplex is developed to block the CCR7‐CCL21 signal and kill tumor cells toward LNs, greatly limiting their lymphatic infiltration. A CCR7‐targeting small interfering RNA (siCCR7) is condensed by mPEG‐poly‐(lysine) with chlorin e6 (Ce6) modification (PPLC) to form PPLC/siCCR7. The knockdown of CCR7 by siCCR7 in tumor cells significantly reduced their response on CCL21 and LN tropism. Additionally, photodynamic therapy‐mediated immune activation precisely targets and kills tumor cells released from the primary foci before they reaches the LNs, reducing the number of tumor cells entering the LNs. Consequently, the PPLC/siCCR7 polyplexes inhibited up to 92% of lung metastasis in 4T1 tumor bearing mice and reduced tumor cell migration to LNs by up to 80%. This site‐specific strategy optimized anti‐metastasis efficacy and promotes the clinical translational development of anti‐metastatic therapy.
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