Chittasupho Chuda, Kewsuwan Prartana, Murakami Takashi
Department of Pharmaceutical Technology, Faculty of Pharmacy, Srinakharinwirot University, Ongkarak, Nakhonnayok, 26120. Thailand.
Thailand Institute of Nuclear Technology, Ongkarak, Nakhonnayok, 26120. Thailand.
Curr Drug Deliv. 2017;14(8):1060-1070. doi: 10.2174/1567201814666170216130448.
CXCR4 possesses a critical role in several intracellular events such as chemotaxis, invasion and adhesion, which are associated with metastasis of cancer cell.
In this study, CXCR4 targeted polymeric nanoparticle was developed for delivering cytotoxic drug and blocking the chemokine induced migration of cells expressing CXCR4.
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.
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.
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.
CXCR4在多种细胞内事件中发挥关键作用,如趋化性、侵袭和黏附,这些都与癌细胞转移相关。
本研究开发了靶向CXCR4的聚合物纳米粒,用于递送细胞毒性药物并阻断趋化因子诱导的表达CXCR4细胞的迁移。
将CXCR4拮抗剂的线性形式(LFC131)肽连接到聚乳酸-羟基乙酸共聚物纳米粒(LFC131-NPs)以及包裹阿霉素的聚乳酸-羟基乙酸共聚物纳米粒(LFC131-DOX-NPs)上。研究了LFC131-DOX-NPs的细胞结合和内化情况。
与未缀合的纳米粒相比,LFC131-DOX-NPs的结合和内化更高且更快。LFC131-NPs阻断了SDF-1α诱导的BT-549-Luc细胞迁移。MTT分析表明,LFC131-NPs和LFC131-DOX-NPs在孵育24、72和120小时后以剂量依赖性方式降低细胞活力。
通过使用LFC131-NPs阻断乳腺癌细胞与SDF-1α相互作用的迁移,然后用阿霉素攻击乳腺癌细胞的治疗理念可能会提高当前乳腺癌治疗的疗效。