Title

CXC chemokine receptor 4 (CXCR4) targeted gold nanoparticles potently enhance radiotherapy outcomes in breast cancer

Document Type

Article

Publication Date

11-25-2021

Publication Title

Nanoscale

Abstract

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.

Medical Subject Headings

Animals; Breast Neoplasms; Cell Line, Tumor; Female; Gold; Humans; Metal Nanoparticles; Mice; Receptors, CXCR4; Triple Negative Breast Neoplasms; Xenograft Model Antitumor Assays

PubMed ID

34757363

Volume

13

Issue

45

First Page

19056

Last Page

19065

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