Department of Pharmaceutical Technology, Faculty of Pharmacy, Srinakharinwirot University, Nakhonnayok 26120, Thailand.
Department of Clinical Microscopy, Division of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50300, Thailand.
Eur J Pharm Biopharm. 2017 Oct;119:310-321. doi: 10.1016/j.ejpb.2017.07.003. Epub 2017 Jul 8.
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.
CXCR4 及其配体 CXCL12 在各种类型的癌症转移中发挥着关键作用，包括乳腺癌。乳腺癌肿瘤优先转移到肺、骨和远处淋巴结，分泌高水平的 CXCL12。我们假设靶向抑制乳腺癌细胞中的 CXCR4 应该抑制 CXCR4 阳性肿瘤细胞向继发性转移部位。在本研究中，研究了携带 DOX 的靶向 CXCR4 的树枝状大分子（LFC131-DOX-D4）对 BT-549-Luc 和 T47D 乳腺癌细胞的细胞结合、细胞毒性和迁移的疗效。用识别乳腺癌细胞表面表达的 CXCR4 的 LFC131 肽对 PAMAM 树枝状大分子进行了表面功能化。LFC131-DOX-D4 与乳腺癌细胞结合，导致体外细胞毒性显著增强，与非靶向树枝状大分子相比。LFC131-D4 显著降低了 BT-549-Luc 乳腺癌细胞向趋化剂的迁移。本报告证明了 LFC131-树枝状大分子缀合物在乳腺癌治疗和转移中的潜在应用。
