金纳米棒、阳离子脂质体和 Pluronic F127 胶束药物载体用于胃癌治疗的 AlPcS-PDT。
AlPcS-PDT for gastric cancer therapy using gold nanorod, cationic liposome, and Pluronic F127 nanomicellar drug carriers.
机构信息
Key Laboratory of Biomedical Information Engineering of Education Ministry, Institute of Biomedical Analytical Technology and Instrumentation, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
School of Innovation and Entrepreneurship, Xi'an Fan Yi University, Xi'an, Shaanxi, China.
出版信息
Int J Nanomedicine. 2018 Apr 4;13:2017-2036. doi: 10.2147/IJN.S154054. eCollection 2018.
PURPOSE
As a promising photodynamic therapy (PDT) agent, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS) provides deep penetration into tissue, high quantum yields, good photostability, and low photobleaching. However, its low delivery efficiency and high binding affinity to serum albumin cause its low penetration into cancer cells, further limiting its PDT effect on gastric cancer. In order to improve AlPcS/PDT effect, the AlPcS delivery sys tems with different drug carriers were synthesized and investigated.
MATERIALS AND METHODS
Gold nanorods, cationic liposomes, and Pluronic F127 nanomicellars were used to formulate the AlPcS delivery systems. The anticancer effect was evaluated by CCK-8 assay and colony formation assay. The delivery efficiency of AlPcS and the binding affinity to serum proteins were determined by fluorescence intensity assay. The apoptosis and necrosis ability, reactive oxygen species and singlet oxygen generation, mitochondrial transmembrane potential and ([Ca]) concentration were further measured to evaluate the mechanism of cell death.
RESULTS
The series of synthesized AlPcS delivery systems with different drug carriers improve the limited PDT effect in varying degrees. In contrast, AlPcS complex with gold nanorods has significant anticancer effects because gold nanorods are not only suitable for AlPcS delivery, but also exhibit enhanced singlet oxygen generation effect and photothermal effect to induce cell death directly. Moreover, AlPcS complex with cationic liposomes shows the potent inhibition effect because of its optimal AlPcS delivery efficiency and ability to block serum albumin. In addition, AlPcS complex with Pluronic F127 exhibits inferior PDT effect but presents lower cytotoxicity, slower dissociation rate, and longer retention time of incorporated drugs; thus, F127-AlPcS is used for prolonged gastric cancer therapy.
CONCLUSION
The described AlPcS drug delivery systems provide promising agents for gastric cancer therapy.
目的
作为一种有前途的光动力疗法（PDT）试剂，铝（III）酞菁四磺酸（AlPcS）提供了组织的深穿透、高量子产率、良好的光稳定性和低光漂白性。然而，其低递送效率和与血清白蛋白的高结合亲和力导致其向癌细胞的低渗透，进一步限制了其对胃癌的 PDT 效果。为了提高 AlPcS/PDT 效果，合成并研究了具有不同药物载体的 AlPcS 递送系统。
材料和方法
使用金纳米棒、阳离子脂质体和 Pluronic F127 纳米胶束来配制 AlPcS 递送系统。通过 CCK-8 测定法和集落形成测定法评估抗癌效果。通过荧光强度测定法测定 AlPcS 的递送效率和与血清蛋白的结合亲和力。进一步测量凋亡和坏死能力、活性氧和单线态氧的产生、线粒体跨膜电位和([Ca])浓度，以评估细胞死亡的机制。
结果
一系列具有不同药物载体的合成 AlPcS 递送系统在不同程度上改善了有限的 PDT 效果。相比之下，与金纳米棒结合的 AlPcS 复合物具有显著的抗癌效果，因为金纳米棒不仅适合 AlPcS 递送，而且还表现出增强的单线态氧产生效应和光热效应，直接诱导细胞死亡。此外，与阳离子脂质体结合的 AlPcS 表现出有效的抑制作用，因为其具有最佳的 AlPcS 递送效率和阻止血清白蛋白的能力。此外，与 Pluronic F127 结合的 AlPcS 表现出较差的 PDT 效果，但表现出较低的细胞毒性、较慢的解离速率和更长的结合药物保留时间；因此，F127-AlPcS 用于延长胃癌治疗。
结论
所描述的 AlPcS 药物递送系统为胃癌治疗提供了有前途的试剂。
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