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Multimodal image-guided folic acid targeted Ag-based quantum dots for the combination of selective methotrexate delivery and photothermal therapy
Journal of Photochemistry and Photobiology B: Biology ( IF 3.9 ) Pub Date : 2020-11-12 , DOI: 10.1016/j.jphotobiol.2020.112082
Mahshid Hashemkhani , Abdullah Muti , Alphan Sennaroğlu , Havva Yagci Acar

Multifunctional quantum dots (QDs) with photothermal therapy (PTT) potential loaded with an anticancer drug and labelled with a targeting agent can be highly effective nano-agents for tumour specific, image-guided PTT/chemo combination therapy of cancer. Ag-chalcogenides are promising QDs with good biocompatibility. Ag2S QDs are popular theranostic agents for imaging in near-infrared with PTT potential. However, theranostic applications of AgInS2 QDs emitting in the visible region and its PTT potential need to be explored. Here, we first present a simple synthesis of small, glutathione (GSH) coated AgInS2 QDs with peak emission at 634 nm, 21% quantum yield, and excellent long-term stability without an inorganic shell. Ag2S-GSH QDs emitting in the near-infrared region (peak emission = 822 nm) were also produced. Both QDs were tagged with folic acid (FA) and conjugated with methotrexate (MTX). About 3-fold higher internalization of FA-tagged QDs by folate-receptor (FR) overexpressing HeLa cells than HT29 and A549 cells was observed. Delivery of MTX by QD-FA-MTX reduced the IC50 of the drug from 10 μg/mL to 2.5–5 μg/mL. MTX release was triggered at acidic pH, which was further enhanced with local temperature increase created by laser irradiation. Irradiation of AgInS2-GSH QDs at 640 nm (300 mW) for 10 min, caused about 10 °C temperature increase but did not cause any thermal ablation of cells. On the other hand, Ag2S-GSH-FA based PTT effectively and selectively killed HeLa cells with 10 min 808 nm laser irradiation via mostly necrosis with an IC50 of 5 μg Ag/mL. Under the same conditions, IC50 of MTX was reduced to 0.21 μg/mL if Ag2S-GSH-FA.



中文翻译:

多峰图像引导的叶酸靶向银基量子点,用于选择性甲氨蝶呤递送和光热疗法的组合

具有光热疗法(PTT)潜能的多功能量子点(QDs)载有抗癌药并用靶向剂标记,可以成为用于肿瘤特异性,图像引导的PTT /化学联合疗法的高效纳米剂。银硫族化物是具有良好生物相容性的有前途的量子点。Ag 2 S QD是用于PTT电位近红外成像的流行的治疗方法。但是,需要探索在可见光区域发射AgInS2 QD的分子筛应用及其PTT潜力。在这里,我们首先介绍一个小的,谷胱甘肽(GSH)包被的AgInS 2的简单合成方法QDs在634 nm处具有峰值发射,量子产率为21%,并且在没有无机壳的情况下具有出色的长期稳定性。还产生了在近红外区域发射的Ag2S-GSH QD(峰值发射= 822 nm)。两个QD均标记有叶酸(FA),并与甲氨蝶呤(MTX)偶联。与HT29和A549细胞相比,通过叶酸受体(FR)过表达的HeLa细胞,FA标记的QD的内在化作用高出约3倍。通过QD-FA-MTX传递MTX可使药物的IC50从10μg/ mL降低至2.5-5μg/ mL。MTX释放是在酸性pH值下触发的,随着激光照射引起的局部温度升高,MTX释放进一步增强。AgInS 2的辐照-GSH QD在640 nm(300 mW)下持续10分钟,引起温度升高约10°C,但未引起细胞热消融。另一方面,基于Ag 2 S-GSH-FA的PTT通过主要坏死,以5μgAg / mL的IC 50通过10分钟808 nm激光辐照有效和选择性地杀死HeLa细胞。在相同条件下,如果使用Ag 2 S-GSH-FA ,MTX的IC 50降低至0.21μg/ mL 。

更新日期:2020-11-19
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