Zinc pthalocyanine-loaded chitosan/mPEG-PLA nanoparticles-mediated photodynamic therapy for the treatment of cutaneous squamous cell carcinoma
Zinc pthalocyanine-loaded chitosan/mPEG-PLA nanoparticles-mediated photodynamic therapy for the treatment of cutaneous squamous cell carcinoma
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负载酞菁锌的壳聚糖/mPEG-PLA纳米粒子介导的光动力疗法用于治疗皮肤鳞状细胞癌。
DOI：
10.1002/jbio.201800114
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发表时间：
2018-11-01
影响因子：
2.8
通讯作者：
Shi, Lei
中科院分区：
文献类型：
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作者：
Keyal, Uma;Luo, Qiong;Shi, Lei
酞菁锌（ZnPc）是第二代光动力治疗（PDT）增敏剂，对鳞状细胞癌（SCC）具有足够的PDT活性。ZnPc疏水且不溶于水，这给全身给药带来了障碍，因此限制了其在临床中的应用。我们将ZnPc负载在壳聚糖/甲氧基聚乙二醇聚乳酸（CPP）纳米颗粒上，形成Z-CPP，以增强PDT的疗效。体外和体内实验观察了化合物ZnPc、CPP和Z-CPP的暗毒性。然后进行PDT实验，观察其对SCC细胞的生长抑制作用。此外，我们还研究了PDT后癌细胞活性氧（ROS）的形成和凋亡情况。结果表明，所测化合物无暗毒性，PDT与Z-CPP的作用效果明显优于游离ZnPc （1 M浓度下p50% ~ 10 M浓度下bbb80 %）。与游离znpc处理的细胞相比，z - cpp处理的细胞凋亡细胞数量最多，产生的ROS也更多(P
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 50% at 1 M to >80% at 10 M concentration. Also Z-CPP-treated cells had highest number of apoptotic cells and produced more ROS compared to free ZnPc-treated cells (P