Chin William W L, Heng Paul W S, Olivo Malini
Division of Medical Sciences, 11 Hospital Drive, Singapore 169610, National Cancer Centre, Singapore.
BMC Pharmacol. 2007 Dec 1;7:15. doi: 10.1186/1471-2210-7-15.
Photodynamic therapy (PDT) is an effective local cancer treatment that involves light activation of a photosensitizer, resulting in oxygen-dependent, free radical-mediated cell death. Little is known about the comparative efficacy of PDT in treating non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), despite ongoing clinical trials treating lung cancers. The present study evaluated the potential use of chlorin e6 - polyvinylpyrrolidone (Ce6-PVP) as a multimodality photosensitizer for fluorescence detection and photodynamic therapy (PDT) on NSCLC and SCLC xenografts.
Human NSCLC (NCI-H460) and SCLC (NCI-H526) tumor cell lines were used to establish tumor xenografts in the chick chorioallantoic membrane (CAM) model as well as in the Balb/c nude mice. In the CAM model, Ce6-PVP was applied topically (1.0 mg/kg) and fluorescence intensity was charted at various time points. Tumor-bearing mice were given intravenous administration of Ce6-PVP (2.0 mg/kg) and laser irradiation at 665 nm (fluence of 150 J/cm2 and fluence rate of 125 mW/cm2). Tumor response was evaluated at 48 h post PDT. Studies of temporal fluorescence pharmacokinetics in CAM tumor xenografts showed that Ce6-PVP has a selective localization and a good accuracy in demarcating NSCLC compared to SCLC from normal surrounding CAM after 3 h post drug administration. Irradiation at 3 h drug-light interval showed greater tumor necrosis against human NSCLC xenografts in nude mice. SCLC xenografts were observed to express resistance to photosensitization with Ce6-PVP.
The formulation of Ce6-PVP is distinctly advantageous as a diagnostic and therapeutic agent for fluorescence diagnosis and PDT of NSCLC.
光动力疗法(PDT)是一种有效的局部癌症治疗方法,它通过光激活光敏剂,导致依赖氧气、自由基介导的细胞死亡。尽管正在进行肺癌的临床试验,但关于PDT治疗非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)的比较疗效知之甚少。本研究评估了二氢卟吩e6 - 聚乙烯吡咯烷酮(Ce6 - PVP)作为一种多模态光敏剂用于NSCLC和SCLC异种移植瘤荧光检测和光动力疗法(PDT)的潜在用途。
使用人NSCLC(NCI - H460)和SCLC(NCI - H526)肿瘤细胞系在鸡胚绒毛尿囊膜(CAM)模型以及Balb/c裸鼠中建立肿瘤异种移植模型。在CAM模型中,局部应用Ce6 - PVP(1.0 mg/kg),并在不同时间点记录荧光强度。给荷瘤小鼠静脉注射Ce6 - PVP(2.0 mg/kg),并在665 nm波长进行激光照射(光通量为150 J/cm²,光通量率为125 mW/cm²)。在PDT后48小时评估肿瘤反应。对CAM肿瘤异种移植瘤进行的时间荧光药代动力学研究表明,给药后3小时,与周围正常CAM中的SCLC相比,Ce6 - PVP在NSCLC中具有选择性定位,并且在区分NSCLC方面具有良好的准确性。在给药后3小时的药物 - 光照间隔进行照射显示,对裸鼠中的人NSCLC异种移植瘤具有更大的肿瘤坏死作用。观察到SCLC异种移植瘤对Ce6 - PVP光致敏表现出抗性。
Ce6 - PVP制剂作为NSCLC荧光诊断和PDT的诊断和治疗剂具有明显优势。