Abstract：
Surface-engineered gold nanoparticles have been considered as versatile systems for theranostics applications. Moreover, surface covering or stabilizing agents on gold nanoparticles especially gold nanobipyramids (AuNBPs) provides an extra space for cargo molecules entrapment. However, it is not well studied yet and also the preparation of AuNBPs still remains dependent largely on cetyltrimethylammonium bromide (CTAB), a cytotoxic surfactant. Therefore, the direct use of CTAB stabilized nanoparticles is not recommended for cancer theranostics applications. Herein, we address an approach of dodecyl ethyl dimethylammonium bromide (DMAB) as biocompatible structure directing agent for AuNBPs, which also accommodate anticancer drug doxorubicin (45%), an additional chemotherapeutics agent. Upon near-infrared light (NIR, 808 nm) exposure, engineered AuNBPs exhibit (i) better phototransduction (51 °C) due to NIR absorption ability (650-900 nm), (ii) photo triggered drug release (more than 80%), and (iii) synergistic chemophototherapy for breast cancer cells. Drug release response has been evaluated in tumor microenvironment conditions (84% in acidic pH and 80% at high GSH) due to protonation and high affinity of thiol binding with AuNBPs followed by DMAB replacement. Intracellular glutathione (GSH, 5-7.5 mM) replaces DMAB from AuNBPs, which cause easy aggregation of nanoparticles as corroborated by colorimetric shifts, suggesting their utilization as a molecular sensing probe of early stage cancer biomarkers. Our optimized recipe yield is monodisperse DMAB-AuNBPs with ∼90% purity even at large scales (500 mL volume per batch). DMAB-AuNBPs show better cell viability (more than 90%) across all concentrations (5-500 ug/mL) when directly compared to CTAB-AuNBPs (less than 10%). Our findings show the potential of DMAB-AuNBPs for early stage cancer detection and theranostics applications.
摘要：
表面工程金纳米颗粒已被认为是治疗应用的通用系统。此外，金纳米颗粒上的表面覆盖剂或稳定剂，尤其是金纳米金字塔（AuNBPs）为货物分子的捕获提供了额外的空间。然而,它还没有很好的研究，而且AuNBPs的制备仍然很大程度上依赖于十六烷基三甲基溴化铵（CTAB），细胞毒性表面活性剂。因此,不建议将CTAB稳定的纳米颗粒直接用于癌症治疗应用。在这里，我们提出了十二烷基乙基二甲基溴化铵（DMAB）作为AuNBPs的生物相容性结构导向剂的方法，也容纳抗癌药物阿霉素（45％），额外的化学治疗剂。在近红外光(NIR，808nm)曝光,工程AuNBPs表现出（i）更好的光转导（51°C）由于近红外吸收能力（650-900nm），（ii）照片触发的药物释放（超过80％），和(iii)乳腺癌细胞的协同化学放射治疗。由于质子化和硫醇与AuNBPs结合的高亲和力，然后进行DMAB置换，已在肿瘤微环境条件下（酸性pH为84％，高GSH为80％）评估了药物释放响应。细胞内谷胱甘肽（GSH，5-7.5mM)取代AuNBPs的DMAB，这导致纳米粒子容易聚集，如色度变化所证实的，表明它们作为早期癌症生物标志物的分子传感探针。我们优化的配方产量是单分散DMAB-AuNBPs，即使在大规模（每批500毫升体积）下，纯度也高达90%。当直接与CTAB-AuNBP(小于10%)相比时,DMAB-AuNBP在所有浓度(5-500ug/mL)中显示出更好的细胞活力(大于90%)。我们的发现显示了DMAB-AuNBPs用于早期癌症检测和治疗应用的潜力。
