CXCR4 targeted dendrimer for anti-cancer drug delivery and breast cancer cell migration inhibition

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Abstract

CXCR4 and its ligand CXCL12 play a critical role in the metastasis of various types of cancer including breast cancer. Breast tumors preferentially metastasize to the lung, bones and distant lymph nodes, secreting high levels of CXCL12. We hypothesized that targeted inhibition of CXCR4 in breast cancer cells should suppress CXCR4-positive tumor cells toward secondary metastatic sites. In the present study, the efficacy of CXCR4 targeted dendrimers carrying DOX (LFC131-DOX-D4) on cellular binding, cytotoxicity, and migration of BT-549-Luc and T47D breast cancer cells was investigated. PAMAM dendrimers encapsulating DOX was surface functionalized with LFC131 peptide which recognized CXCR4 expressed on the surface of breast cancer cells. The LFC131-DOX-D4 bound to breast cancer cells resulting in significantly enhanced in vitro cellular toxicity as compared with non-targeted dendrimers. The LFC131-D4 exhibited remarkable reduced migration of BT-549-Luc breast cancer cells toward chemoattractant. This report demonstrated the potential utility of LFC131-dendrimer conjugates for breast cancer therapy and metastasis.

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