School of Pharmacy, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi-do 16419, Republic of Korea.
College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyongsan 38541, Republic of Korea.
Int J Pharm. 2018 Dec 20;553(1-2):363-374. doi: 10.1016/j.ijpharm.2018.10.063. Epub 2018 Oct 29.
Gold nanoclusters (AuNCs) have been considered to be a promising candidate for hyperthermia-based anticancer therapy. Herein, we introduce albumin-assisted AuNCs composed of small gold nanoparticles (AuNPs, <6 nm) assembled with strands of polyallylamine (PAH), which exhibited strong surface plasmon resonance upon near-infrared (NIR, ∼808 nm) laser irradiation and good in vivo stability. Our albumin-assisted PAH-AuNCs (BSA/PAH-AuNCs) were facilely fabricated as a top-down process by a simple ultrasonication after the preparation of large nano-aggregates of PAH-AuNPs. Albumin played a critical role as a stabilizer and surfactant in making loosely associated large aggregates and thereby producing small gold nanoclusters (∼60 nm) of slightly negative charge upon ultrasonication. The prepared BSA/PAH-AuNCs displayed excellent hyperthermal effects (∼60 °C) in response to ∼808-nm NIR laser irradiation in a 4T1 cell system in vitro and in 4T1 cell tumor xenograft mice in vivo, indicating their remarkable potential to suppress breast cancer growth, without almost no significant toxicity in histology. Consequently, our gold nanoclusters should be considered as a promising photothermal agent that are easy to manufacture and exhibit marked anticancer effects in terms of tumor ablation.
金纳米簇(AuNCs)被认为是一种很有前途的基于热疗的抗癌治疗候选物。在此,我们介绍了由小金纳米粒子(AuNPs,<6nm)与多聚烯丙胺(PAH)链组装而成的白蛋白辅助 AuNCs,其在近红外(NIR,∼808nm)激光照射下表现出强的表面等离子体共振,并且具有良好的体内稳定性。我们的白蛋白辅助 PAH-AuNCs(BSA/PAH-AuNCs)是通过简单的超声处理,在制备大的 PAH-AuNP 纳米聚集体之后,很容易采用自上而下的方法制备。白蛋白在使大的聚集物松散结合以及在超声处理时产生略带负电荷的小金纳米簇(∼60nm)方面发挥了关键作用。所制备的 BSA/PAH-AuNCs 在体外 4T1 细胞系统和体内 4T1 细胞肿瘤异种移植小鼠中对∼808nm 的近红外激光照射表现出优异的热效应(∼60°C),表明其具有显著抑制乳腺癌生长的潜力,在组织学上几乎没有明显的毒性。因此,我们的金纳米簇应该被认为是一种很有前途的光热试剂,它们易于制造,并具有显著的肿瘤消融抗癌效果。