Department of Genome Integrity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.
Int J Nanomedicine. 2021 May 18;16:3407-3427. doi: 10.2147/IJN.S304953. eCollection 2021.
Plasmonic photothermal cancer therapy by gold nanorods (GNRs) emerges as a promising tool for cancer treatment. The goal of this study was to design cationic oligoethylene glycol (OEG) compounds varying in hydrophobicity and molecular electrostatic potential as ligand shells of GNRs. Three series of ligands with different length of OEG chain (ethylene glycol units = 3, 4, 5) and variants of quaternary ammonium salts (QAS) as terminal functional group were synthesized and compared to a prototypical quaternary ammonium ligand with alkyl chain - (16-mercaptohexadecyl)trimethylammonium bromide (MTAB).
Step-by-step research approach starting with the preparation of compounds characterized by NMR and HRMS spectra, GNRs ligand exchange evaluation through characterization of cytotoxicity and GNRs cellular uptake was used. A method quantifying the reshaping of GNRs was applied to determine the effect of ligand structure on the heat transport from GNRs under fs-laser irradiation.
Fourteen out of 18 synthesized OEG compounds successfully stabilized GNRs in the water. The colloidal stability of prepared GNRs in the cell culture medium decreased with the number of OEG units. In contrast, the cellular uptake of GNRs by HeLa cells increased with the length of OEG chain while the structure of the QAS group showed a minor role. Compared to MTAB, more hydrophilic OEG compounds exhibited nearly two order of magnitude lower cytotoxicity in free state and provided efficient cellular uptake of GNRs close to the level of MTAB. Regarding photothermal properties, OEG compounds evoked the photothermal reshaping of GNRs at lower peak fluence (14.8 mJ/cm) of femtosecond laser irradiation than the alkanethiol MTAB.
GNRs appear to be optimal for clinical applications with systemic administration of NPs not-requiring irradiation at high laser intensity such as drug delivery and photothermal therapy inducing apoptosis.
金纳米棒（GNRs）的等离子体光热癌症治疗作为癌症治疗的一种有前途的工具而出现。本研究的目的是设计疏水性和分子静电势不同的阳离子聚乙二醇（OEG）化合物作为 GNRs 的配体壳。合成了具有不同 OEG 链长度（乙二醇单元= 3、4、5）和季铵盐（QAS）变体的三个系列配体，并将其与具有烷基链的典型季铵配体 - （16-巯基十六烷基）三甲基溴化铵（MTAB）进行了比较。
使用逐步研究方法，从化合物的制备开始，通过 NMR 和 HRMS 光谱进行表征，通过细胞毒性和 GNRs 细胞摄取的表征来评估 GNRs 配体交换，应用定量方法来确定配体结构对 fs-激光照射下从 GNRs 传输热量的影响。
18 种合成的 OEG 化合物中有 14 种成功地在水中稳定了 GNRs。制备的 GNRs 在细胞培养基中的胶体稳定性随 OEG 单元数的增加而降低。相比之下，HeLa 细胞对 GNRs 的细胞摄取随 OEG 链的长度增加而增加，而 QAS 基团的结构则作用较小。与 MTAB 相比，更亲水的 OEG 化合物在游离状态下表现出近两个数量级的低细胞毒性，并提供了接近 MTAB 水平的 GNRs 的有效细胞摄取。关于光热特性，OEG 化合物在皮秒激光照射的较低峰值强度（14.8 mJ/cm）下引起 GNRs 的光热重塑，低于烷硫醇 MTAB。
GNRs 似乎是最适合临床应用的，通过全身给药 NPs 不需要在高激光强度下进行照射，例如药物输送和光热治疗诱导细胞凋亡。
