癌症研究
三阴性乳腺癌
CXCR4型
趋化因子受体
趋化因子受体
乳腺癌
癌细胞
趋化因子
受体
化学
作者
Shanta Raj Bhattarai,Yuri Mackeyev,Bhanu Prasad Venkatesulu,Sunil Krishnan,Pankaj Singh
出处
期刊:Nanoscale
[The Royal Society of Chemistry]
日期:2021-11-25
卷期号:13 (45): 19056-19065
摘要
CXC chemokine receptor 4 (CXCR4) is overexpressed on most breast cancer cell surfaces including triple negative breast cancer (TNBC) which lacks traditional receptor overexpression. We targeted gold nanoparticles (GNPs) to this receptor via conjugation to anti-CXCR4 antibody (cGNPs). Irradiation of cells treated with cGNPs compared to PEGylated GNPs (pGNPs) resulted in more prominent radiosensitization of MDA-MB-231 cells with abundant CXCR4 overexpression than HTB-123 cells with moderate and MCF-7 cells with minimal CXCR4 overexpression. Overexpression of CXCR4 facilitated improved cellular internalization of cGNPs and irradiation of internalized cGNPs resulted in more unrepaired DNA double strand breaks and increased the production of oxygen free radicals compared to irradiation with non-internalized pGNPs. In a murine TNBC xenograft model, CXCR4 targeting potently increased tumor regrowth delay following radiation compared to radiation in the presence of pGNPs or vehicle alone. CXCR4 targeted GNPs enhance the efficacy of TNBC radiotherapy by increasing oxidative stress and DNA damage.
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