Saravanakumar Kandasamy, Sathiyaseelan Anbazhagan, Zhang Xin, Park Soyoung, Wang Myeong-Hyeon
Department of Bio-Health Convergence, Kangwon National University, Chuncheon 200-701, Korea.
Pharmaceuticals (Basel). 2022 May 6;15(5):582. doi: 10.3390/ph15050582.
The adenosine triphosphate (ATP)-conjugated biogenic selenium nanoparticles (SeNPs) for P2 (purinoceptors) receptor-targeted anti-colon cancer activity were developed in this study. First, the SeNPs were synthesized using extracts (TE) and then conjugated with ATP to enhance their anticancer activity. The developed SeNPs had an oval crystalline structure with an average diameter size of 26.45 ± 1.71 d. nm, while the ATP-SeNPs were 78.6 ± 2.91 d. nm. The SeNPs contain Se, and less persistence of P while the ATP-SeNPs have high level of P, and Se in the energy-dispersive spectroscopy (EDS). Further, both nanoparticles exhibited larger sizes in the dynamic light scattering (DLS) analysis than in the transmission electron microscopy (TEM) analysis. The DLS and Fourier transform infrared spectroscopy (FTIR) results provide evidence that the amine group (-NH) of ATP might bind with the negatively charged SeNPs through covalent bonding. The IC concentration was 17.25 ± 1.16 µg/mL for ATP-SeNPs and 61.24 ± 2.08 µg/mL against the caco-2 cell line. The IC results evidenced the higher cytotoxicity of ATP-SeNPs in the caco-2 cell line than in HEK293 cells. ATP-SeNPs trigger the anticancer activity in the caco-2 cell line through the induction of mitochondrial membrane potential (MMP) loss and nucleus damage. The biocompatibility test of hemolysis and the egg CAM assay confirmed the non-toxicity of these nanoparticles. Overall, the results proved that the newly developed ATP-SeNPs exhibited higher cytotoxicity in the caco-2 cell line than SeNPs. However, further molecular and in vivo experiments are required to develop the ATP-SeNPs as a candidate drug for cancer-targeted therapeutics.
本研究开发了用于P2(嘌呤受体)受体靶向抗结肠癌活性的三磷酸腺苷(ATP)共轭生物源硒纳米颗粒(SeNPs)。首先,使用提取物(TE)合成SeNPs,然后与ATP共轭以增强其抗癌活性。所开发的SeNPs具有椭圆形晶体结构,平均直径大小为26.45±1.71 d.nm,而ATP-SeNPs为78.6±2.91 d.nm。SeNPs含有Se,而P的含量较低,而在能量色散光谱(EDS)中,ATP-SeNPs具有高水平的P和Se。此外,在动态光散射(DLS)分析中,两种纳米颗粒的尺寸均比透射电子显微镜(TEM)分析中的尺寸大。DLS和傅里叶变换红外光谱(FTIR)结果提供了证据,表明ATP的胺基(-NH)可能通过共价键与带负电荷的SeNPs结合。ATP-SeNPs对caco-2细胞系的IC浓度为17.25±1.16μg/mL,对HEK293细胞系的IC浓度为61.24±2.08μg/mL。IC结果证明,ATP-SeNPs在caco-2细胞系中的细胞毒性高于HEK293细胞。ATP-SeNPs通过诱导线粒体膜电位(MMP)丧失和细胞核损伤,触发caco-2细胞系中的抗癌活性。溶血生物相容性试验和鸡胚绒毛尿囊膜试验证实了这些纳米颗粒的无毒性。总体而言,结果证明新开发的ATP-SeNPs在caco-2细胞系中比SeNPs表现出更高的细胞毒性。然而,需要进一步的分子和体内实验,以将ATP-SeNPs开发成为癌症靶向治疗的候选药物。