Innovative Research Laboratory for Wound Healing, Health Sciences Department, Università del Piemonte Orientale, via Solaroli, 17, 28100 Novara, Italy.
Dipartimento di Scienze e Innovazione Tecnologica e Centro Nano-SiSTeMI, Università del Piemonte Orientale, V. Teresa Michel 11, 15121 Alessandria, Italy; Nucleos Research of Photodynamic Therapy, Chemistry Department, State University of Maringá, Av. Colombo 5.790, 87020-900 Maringá, Paraná, Brazil.
J Photochem Photobiol B. 2017 Feb;167:1-6. doi: 10.1016/j.jphotobiol.2016.12.021. Epub 2016 Dec 22.
Photodinamic therapy (PDT) has gained an increasing interest as a new tool to treat skin cancers such as melanoma. This clinical approach take advantage from the combination of a photosensitizer and a specific light wavelength able to induce singlet oxygen production. Mesoporous silica nanoparticles (MSNs) have been widely investigated as drug nanocarriers as their structure and morphology could be customized to produce suitable nanoplatforms enabling high cargo capacity. In the present study MSNs were successfully conjugated with the second generation photosensitizer verteporfin and the resulting nanoplatform (Ver-MSNs) was tested in an in vitro PDT model as a potential tool for melanoma treatment. Ver-MSNs based PDT did not affect cell proliferation of neither a normal human keratinocyte cell line (HaCaT) or a low mestastatic melanoma cell line (A375P). On the other hand Ver-MSNs based PDT deeply affect the highly invasive SK-MEL-28 melanoma cell line behavior, as testified by the strong reduction in cell proliferation along with the dramatic change in cellular morphology, through a nanoparticle internalization dependent mechanism. In fact, experiments performed in the presence of endocytosis inhibitors (chlorpromazine and amiloride) resulted in an attenuation of Ver-MSNs based PDT induced cell death, along with a recover in cellular morphology. MSN doped with verteporfin could thus represent a promising and useful tool for PDT treatment of highly invasive melanoma.
光动力学疗法（PDT）作为一种治疗皮肤癌（如黑色素瘤）的新工具，已经引起了越来越多的关注。这种临床方法利用光敏剂和特定波长的光结合，能够诱导单线态氧的产生。介孔硅纳米粒子（MSNs）作为药物纳米载体得到了广泛的研究，因为它们的结构和形态可以定制，以产生合适的纳米平台，从而实现高载药量。在本研究中，MSNs 成功地与第二代光敏剂维替泊芬结合，所得的纳米平台（Ver-MSNs）在体外 PDT 模型中进行了测试，作为治疗黑色素瘤的潜在工具。Ver-MSNs 基 PDT 既不影响正常人类角质形成细胞系（HaCaT）也不影响低转移性黑色素瘤细胞系（A375P）的细胞增殖。另一方面，Ver-MSNs 基 PDT 对高度侵袭性的 SK-MEL-28 黑色素瘤细胞系的行为有很大的影响，这可以通过强烈降低细胞增殖以及通过纳米颗粒内化依赖的机制导致细胞形态的剧烈变化来证明。事实上，在存在内吞作用抑制剂（氯丙嗪和氨甲喋呤）的情况下进行的实验导致 Ver-MSNs 基 PDT 诱导的细胞死亡减弱，同时细胞形态得到恢复。因此，掺杂维替泊芬的 MSN 可能成为治疗高度侵袭性黑色素瘤的 PDT 的一种有前途和有用的工具。
