Inhibiting Metastatic Breast Cancer Cell Migration via the Synergy of Targeted, pH-triggered siRNA Delivery and Chemokine Axis Blockade | Zendy

Peng Guo | Zendy; JinOh You | Zendy; Jiang Yang | Zendy; Di Jia | Zendy; Marsha A. Moses | Zendy; Debra T. Auguste | Zendy

Open Access

Inhibiting Metastatic Breast Cancer Cell Migration via the Synergy of Targeted, pH-triggered siRNA Delivery and Chemokine Axis Blockade

Author(s) -

Peng Guo,

JinOh You,

Jiang Yang,

Di Jia,

Marsha A. Moses,

Debra T. Auguste

Publication year - 2014

Publication title -

molecular pharmaceutics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.13

H-Index - 127

eISSN - 1543-8392

pISSN - 1543-8384

DOI - 10.1021/mp4004699

Subject(s) - blockade , metastatic breast cancer , cxcr4 , cancer research , chemokine , metastasis , triple negative breast cancer , chemokine receptor , breast cancer , gene silencing , cancer , chemistry , cancer cell , cell migration , medicine , pharmacology , immunology , cell , receptor , biochemistry , gene

Because breast cancer patient survival inversely correlates with metastasis, we engineered vehicles to inhibit both the C-X-C chemokine receptor type 4 (CXCR4) and lipocalin-2 (Lcn2) mediated migratory pathways. pH-responsive liposomes were designed to protect and trigger the release of Lcn2 siRNA. Liposomes were modified with anti-CXCR4 antibodies to target metastatic breast cancer (MBC) cells and block migration along the CXCR4-CXCL12 axis. This synergistic approach--coupling the CXCR4 axis blockade with Lcn2 silencing--significantly reduced migration in triple-negative human breast cancer cells (88% for MDA-MB-436 and 92% for MDA-MB-231). The results suggested that drug delivery vehicles engineered to attack multiple migratory pathways may effectively slow progression of MBC.

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