Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA.
Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA.
Biosens Bioelectron. 2017 May 15;91:780-787. doi: 10.1016/j.bios.2017.01.049. Epub 2017 Jan 24.
Targeted drug delivery systems using nanoparticle nanocarriers offer remarkable promise for cancer therapy by discriminating against devastating cytotoxicity of chemotherapeutic drugs to healthy cells. To aid in the development of new drug nanocarriers, we propose a novel plasmonic nanocarrier grid-enhanced Raman sensor which can be applied for studies and testing of drug loading onto the nanocarriers, attachment of targeting ligands, dynamics of drug release, assessment of nanocarrier stability in biological environment, and general capabilities of the nanocarrier. The plasmonic nanogrid sensor offers strong Raman enhancement due to the overlapping plasmonic fields emanating from the nearest-neighbor gold nanoparticle nanocarriers and creating the enhancement "hot spots". The sensor has been tested for immobilization of an anticancer drug gemcitabine (2',2'-difluoro-2'-deoxycytidine, GEM) which is used in treatment of pancreatic tumors. The drawbacks of currently applied treatment include high systemic toxicity, rapid drug decay, and low efficacy (ca. 20%). Therefore, the development of a targeted GEM delivery system is highly desired. We have demonstrated that the proposed nanocarrier SERS sensor can be utilized to investigate attachment of targeting ligands to nanocarriers (attachment of folic acid ligand recognized by folate receptors of cancer cells is described). Further testing of the nanocarrier SERS sensor involved drug release induced by lowering pH and increasing GSH levels, both occurring in cancer cells. The proposed sensor can be utilized for a variety of drugs and targeting ligands, including those which are Raman inactive, since the linkers can act as the Raman markers, as illustrated with mercaptobenzoic acid and para-aminothiophenol.
基于纳米载体的靶向药物投递系统通过区分化疗药物对健康细胞的毁灭性细胞毒性，为癌症治疗带来了显著的希望。为了帮助开发新的药物纳米载体，我们提出了一种新型的等离子体纳米载体网格增强拉曼传感器，该传感器可用于研究和测试药物负载到纳米载体上、靶向配体的附着、药物释放动力学、纳米载体在生物环境中的稳定性评估以及纳米载体的一般性能。由于来自最近邻金纳米载体的等离子体场重叠并产生增强“热点”，等离子体纳米栅格传感器提供了很强的拉曼增强。该传感器已经过测试，用于固定抗癌药物吉西他滨（2'，2'-二氟-2'-脱氧胞苷，GEM），该药物用于治疗胰腺肿瘤。目前应用的治疗方法存在一些缺点，包括全身毒性高、药物迅速衰减和疗效低（约 20%）。因此，开发靶向 GEM 递药系统是非常需要的。我们已经证明，所提出的纳米载体 SERS 传感器可用于研究靶向配体与纳米载体的附着（描述了识别癌细胞叶酸受体的叶酸配体的附着）。进一步测试纳米载体 SERS 传感器涉及通过降低 pH 值和增加 GSH 水平诱导的药物释放，这两种情况都发生在癌细胞中。所提出的传感器可用于各种药物和靶向配体，包括那些拉曼不活跃的药物，因为接头可以作为拉曼标记物，如巯基苯甲酸和对氨基苯硫酚所示。
