叶酸修饰的金光敏纳米颗粒增强LNCaP前列腺癌细胞系的放射敏感性
Enhanced radiosensitivity of LNCaP prostate cancer cell line by gold-photoactive nanoparticles modified with folic acid.
作者信息
Changizi Olya, Khoei Samideh, Mahdavian Alireza, Shirvalilou Sakine, Mahdavi Seied Rabi, Keyvan Rad Jaber
机构信息
Student Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran; Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
出版信息
Photodiagnosis Photodyn Ther. 2020 Mar;29:101602. doi: 10.1016/j.pdpdt.2019.101602. Epub 2019 Nov 14.
BACKGROUND
Conventional cancer treatment methods suffer from many limitations such as non-specificity in discrimination between healthy and malignant cells. The aim of this study was to investigate the role of polymeric gold-photoactive nanoparticles (PGPNPs) conjugated with folic acid (FA) as theranostic nanoparticles for active targeting, real-time fluorescence tracing and radiosensitivity inducition in LNCaP prostate cancer cells.
METHODS
The cellular uptake and cytotoxicity effect of gold nanoparticles (PGPNPs and PGPNPs-FA) after 2 and 24 h treatment were evaluated in in both cancer (LNCaP) and normal (HUVEC) cells using fluorescent microscopy, Induced coupled plasma optical emission spectrometry (ICP-OES) and Tetrazolium bromide dye (MTT), respectively. The therapeutic efficacy was analyzed on the LNCaP cells. For this purpose, LNCaP cells were treated by nanoparticles and ionizing radiation, and the synergistic effect of treatment methods were evaluated by colony formation assay (CFA) and Flow cytometry analysis.
RESULTS
The results of fluorescence imaging and ICP-OES data showed that the LNCaP cells absorbed PGPNP-FA nanoparticles more than PGPNP (P < 0.001). Also, the uptake of nanoparticles was significantly greater in cancer cells than in healthy ones (P < 0.01). MTT assay results indicated higher cytotoxic effect of nanoparticles conjugated with FA in folate-receptor overexpressing LNCaP cancer cells compared to HUVEC normal cells (P < 0.01). Furthermore, CFA and Flow cytometry results demonstrated that combinatorial therapy of polymeric gold nanoparticles with/without FA and ionizing radiation at various doses (2, 4 and 6 Gy) had a synergistic effect on survival fraction and induction of apoptotic and necrotizing cell death (P < 0.01).
CONCLUSION
PGPNPs-FA nanoparticles led to higher and more specific uptake and accumulation of nanoparticles in LNCaP cells, thereby increasing the ability of gold nanoparticles as radio-sensitizer.
背景
传统癌症治疗方法存在诸多局限性，如在区分健康细胞和恶性细胞时缺乏特异性。本研究旨在探讨叶酸（FA）偶联的聚合物金光活性纳米颗粒（PGPNPs）作为治疗诊断纳米颗粒在LNCaP前列腺癌细胞中进行主动靶向、实时荧光追踪和诱导放射敏感性的作用。
方法
分别使用荧光显微镜、电感耦合等离子体发射光谱法（ICP - OES）和四唑溴盐染料（MTT），评估了金纳米颗粒（PGPNPs和PGPNPs - FA）在处理2小时和24小时后对癌症（LNCaP）细胞和正常（HUVEC）细胞的细胞摄取和细胞毒性作用。对LNCaP细胞的治疗效果进行了分析。为此，用纳米颗粒和电离辐射处理LNCaP细胞，并通过集落形成试验（CFA）和流式细胞术分析评估治疗方法的协同作用。
结果
荧光成像和ICP - OES数据结果显示，LNCaP细胞对PGPNP - FA纳米颗粒的吸收多于PGPNP（P < 0.001）。此外，癌细胞对纳米颗粒的摄取明显高于健康细胞（P < 0.01）。MTT试验结果表明，与HUVEC正常细胞相比，在叶酸受体过表达的LNCaP癌细胞中，与FA偶联的纳米颗粒具有更高的细胞毒性作用（P < 0.01）。此外，CFA和流式细胞术结果表明，不同剂量（2、4和6 Gy）的含或不含FA的聚合物金纳米颗粒与电离辐射的联合治疗对存活分数以及凋亡和坏死性细胞死亡的诱导具有协同作用（P < 0.01）。
结论
PGPNPs - FA纳米颗粒导致纳米颗粒在LNCaP细胞中更高且更特异性的摄取和积累，从而提高了金纳米颗粒作为放射增敏剂的能力。
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