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载锌酞菁壳聚糖/ mPEG-PLA 纳米粒介导光动力疗法治疗皮肤鳞状细胞癌。

Zinc pthalocyanine-loaded chitosan/mPEG-PLA nanoparticles-mediated photodynamic therapy for the treatment of cutaneous squamous cell carcinoma.

机构信息

Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, P. R. China.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Shanghai, P. R. China.

出版信息

J Biophotonics. 2018 Nov;11(11):e201800114. doi: 10.1002/jbio.201800114. Epub 2018 Jul 13.

Abstract

Zinc pthalocyanine (ZnPc) is a second-generation photodynamic therapy (PDT) sensitizer with sufficient PDT activity for squamous cell carcinoma (SCC). ZnPc is hydrophobic and insoluble in water, which creates hurdles in systemic administration and hence restricts its use in clinic. Here we have loaded ZnPc on chitosan/methoxy polyethylene glycol-polylactic acid (CPP) nanoparticles to form Z-CPP to enhance PDT efficacy. In vitro and in vivo studies were performed to see dark toxicity of the compounds ZnPc, CPP and Z-CPP. Then PDT was done and its growth inhibitory effect on SCC cells was evaluated. In addition, reactive oxygen species (ROS) formation and apoptosis of cancer cells following PDT were studied. The results showed that the tested compounds exhibit no dark toxicity and the effect of PDT was significantly better with Z-CPP when compared to free ZnPc (P < .05). Photoactivation of Z-CPP led to a dose-dependent growth inhibition of cancer cells of >50% at 1 μM to >80% at 10 μM concentration. Also Z-CPP-treated cells had highest number of apoptotic cells and produced more ROS compared to free ZnPc-treated cells (P < .05). Hence, this study suggests that Z-CPP is a suitable pharmaceutical compound to increase PDT efficacy.

摘要

锌酞菁(ZnPc)是第二代光动力疗法(PDT)敏化剂,对鳞状细胞癌(SCC)具有足够的 PDT 活性。ZnPc 具有疏水性,不溶于水,这在系统给药方面造成了障碍,因此限制了其在临床中的应用。在这里,我们将 ZnPc 负载到壳聚糖/甲氧基聚乙二醇-聚乳酸(CPP)纳米颗粒上,形成 Z-CPP,以提高 PDT 疗效。进行了体外和体内研究,以观察化合物 ZnPc、CPP 和 Z-CPP 的暗毒性。然后进行 PDT,并评估其对 SCC 细胞的生长抑制作用。此外,研究了 PDT 后癌细胞中活性氧(ROS)的形成和细胞凋亡。结果表明,测试的化合物没有暗毒性,与游离 ZnPc 相比,Z-CPP 的 PDT 效果明显更好(P<.05)。Z-CPP 的光激活导致在 1 μM 浓度时癌细胞的生长抑制率>50%,在 10 μM 浓度时>80%。此外,与游离 ZnPc 处理的细胞相比,Z-CPP 处理的细胞具有更高数量的凋亡细胞,并且产生更多的 ROS(P<.05)。因此,这项研究表明 Z-CPP 是一种合适的药物化合物,可以提高 PDT 疗效。

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