Pharmaceutical Technology, School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva 4, Switzerland.
Laboratory of Colloid and Surface Chemistry, Department of Chemistry, University of Geneva, Geneva 4, Switzerland.
Nanomedicine. 2019 Jan;15(1):243-251. doi: 10.1016/j.nano.2018.09.013. Epub 2018 Oct 7.
Novel nanoscale drug delivery biomaterials are of great importance for the diagnosis and treatment of different cancers. We have developed a new pegylated squalene (SQ-PEG) derivative with self-assembly properties. Supramolecular assembly with a lipophilic photosensitizer pyropheophorbide-a (Ppa) by nanoprecipitation gave nanoconstructs SQ-PEG:Ppa with an average size of 200 nm in diameter and a drug loading of 18% (w/w). The composite material demonstrates nanoscale optical properties by tight packing of Ppa within Sq-PEG:Ppa resulting in 99.99% fluorescence self-quenching. The biocompatibility of the nanomaterial and cell phototoxicity under light irradiation were investigated on PC3 prostate tumor cells in vitro. SQ-PEG:Ppa showed excellent phototoxic effect at low light dose of 5.0 J/cm as a consequence of efficient cell internalization of Ppa by the nanodelivery system. The diagnostic potential of SQ-PEG:Ppa nanoconstructs to deliver Ppa to tumors in vivo was demonstrated in chick embryo model implanted with U87MG glioblastoma micro tumors.
新型纳米药物输送生物材料对于不同癌症的诊断和治疗具有重要意义。我们开发了一种具有自组装特性的新型聚乙二醇化角鲨烯（SQ-PEG）衍生物。通过纳米沉淀，超分子组装具有亲脂性光敏剂原卟啉-a（Ppa）的纳米结构 SQ-PEG：Ppa 的平均粒径为 200nm，载药量为 18%（w/w）。由于 Ppa 在 Sq-PEG：Ppa 内的紧密堆积，复合材料表现出纳米级光学特性，导致 99.99%的荧光自猝灭。体外研究了纳米材料的生物相容性和光照射下的细胞光毒性在 PC3 前列腺肿瘤细胞上。SQ-PEG：Ppa 在 5.0J/cm2 的低光剂量下表现出优异的光毒性效应，这是由于纳米递药系统能够有效地将 Ppa 内吞到细胞内。SQ-PEG：Ppa 纳米结构将 Ppa 递送至体内肿瘤的诊断潜力在植入 U87MG 神经胶质瘤微肿瘤的鸡胚模型中得到了证明。
