Abstract
Background: CXCR4 possesses a critical role in several intracellular events such as chemotaxis, invasion and adhesion, which are associated with metastasis of cancer cell.
Objective: In this study, CXCR4 targeted polymeric nanoparticle was developed for delivering cytotoxic drug and blocking the chemokine induced migration of cells expressing CXCR4.
Method: A peptide which was a linear form of CXCR4 antagonist (LFC131) was attached to PLGA nanoparticles (LFC131-NPs) and PLGA nanoparticles encapsulating DOX (LFC131-DOX-NPs). The cellular binding and internalization of LFC131-DOX-NPs were investigated.
Results: The binding and internalization of LFC131-DOX-NPs were higher and more rapidly compared to unconjugated NPs. LFC131-NPs blocked SDF-1α induced migration of BT-549-Luc cells. MTT assays demonstrated that LFC131-NPs and LFC131-DOX-NPs decreased cell viability in a dose dependent manner in 24, 72 and 120 h incubation.
Conclusion: A treatment concept of blocking breast cancer cell migration from interaction with SDF- 1α by using LFC131-NPs and then attacking breast cancer cells with doxorubicin might increase the efficacy of current breast cancer treatment.
Keywords: Breast cancer, CXCR4, LFC131, metastasis, nanoparticle, PLGA.
Graphical Abstract
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