Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Colloids Surf B Biointerfaces. 2017 Dec 1;160:715-723. doi: 10.1016/j.colsurfb.2017.10.027. Epub 2017 Oct 9.
The use of gold nanorods (AuNRs) that produce heat in response to near infrared (NIR) irradiation is an attractive approach to cancer photothermal therapy. AuNRs are usually prepared by using a highly toxic detergent: cetyltrimethylammonium bromide (CTAB). Thus, the removal of CTAB from the reaction mixture, and further stabilization of the surface of the AuNRs is required. In the present study, AuNRs were encapsulated in a multifunctional envelope-type nano device (AuNR-MEND) formed with an SS-cleavable and pH-activated lipid-like material. In the process of encapsulation, AuNRs were first stabilized with bovine serum albumin (AuNR-BSA), and then further encapsulated in the lipid envelope by the ethanol dilution method. The in vitro photothermal cytotoxicity of AuNR-MEND was further demonstrated on 4T1 breast cancer cells. After NIR radiation, the temperature of the medium was increased to approximately 60°C, and cell viability was drastically decreased to approximately 11%. However, this cytotoxic effect cannot simply be explained by medium heating. It therefore appears that intracellular delivery of the AuNRs is a key factor for achieving a high degree of cytotoxicity. Dose dependent cytotoxicity data revealed that a higher dose of AuNR-MEND resulted in the complete destruction of the cells when they were subjected to NIR irradiation, while the cell survival rate reached a plateau at 30% in the case of AuNR-BSA. Apoptosis was induced after treatment with the nanoparticles. AuNR-MEND showed superior cellular uptake activity over AuNR-BSA. Thus, delivering AuNR by means of functionalized lipid nanoparticles represents a promising approach to induce NIR-triggered apoptosis.
金纳米棒(AuNRs)在近红外(NIR)照射下产生热量,这是一种有吸引力的癌症光热治疗方法。AuNRs 通常通过使用一种剧毒的洗涤剂:十六烷基三甲基溴化铵(CTAB)来制备。因此,需要从反应混合物中去除 CTAB,并进一步稳定 AuNRs 的表面。在本研究中,AuNRs 被包裹在一种多功能信封型纳米装置(AuNR-MEND)中,该装置由 SS 可切割和 pH 激活的类脂质材料形成。在封装过程中,AuNRs 首先用牛血清白蛋白(AuNR-BSA)稳定,然后通过乙醇稀释法进一步包裹在脂质包膜中。AuNR-MEND 的体外光热细胞毒性进一步在 4T1 乳腺癌细胞上得到证明。在 NIR 辐射后,介质的温度升高到约 60°C,细胞活力急剧下降到约 11%。然而,这种细胞毒性效应不能简单地用介质加热来解释。因此,似乎细胞内递送 AuNRs 是实现高细胞毒性的关键因素。剂量依赖性细胞毒性数据表明,当 AuNR-MEND 受到 NIR 照射时,更高剂量的 AuNR-MEND 导致细胞完全破坏,而 AuNR-BSA 的细胞存活率在 30%时达到平台期。纳米颗粒处理后诱导细胞凋亡。AuNR-MEND 显示出优于 AuNR-BSA 的细胞摄取活性。因此,通过功能化脂质纳米颗粒递送 AuNR 代表了一种有前途的方法,可以诱导 NIR 触发的细胞凋亡。