Faculty of Chemical Engineering, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic.
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, v.v.i, Heyrovskéhonám. 2, 162 06 Prague 6, Czech Republic.
J Control Release. 2016 Nov 10;241:34-44. doi: 10.1016/j.jconrel.2016.09.009. Epub 2016 Sep 10.
We developed fully biodegradable/metabolizable nanosystem based on polymer surfactant-stabilized thermoresponsive solid lipid nanoparticles with non-covalently bound photosensitizer temoporfin (T-SLNP) with particle size below 50nm. The efficacy of T-SLNP was compared with commercial temoporfin formulation in terms of in vitro phototoxicity in 4T1 (murine mammary carcinoma) and MDA-MB-231(human breast adenocarcinoma) cells and of in vivo anticancer effect in Nu/Nu mice bearing MDA-MB-231 tumors. In vitro study demonstrated faster accumulation kinetics in the cells for our formulation design resulting in higher phototoxicity against the tumor cells. In vivo anticancer efficacy was markedly improved by T-SLNP compared with commercial temoporfin formulation. Owing to controlled and sustained release properties, subcellular size, biocompatibility with tissue and cells, the T-SLNP nanodispersion prepared in this study represents promising drug delivery system applicable in cancer treatment.
我们开发了一种完全可生物降解/可代谢的纳米系统,该系统基于聚合物表面活性剂稳定的温敏性固体脂质纳米粒子,其中结合了非共价键结合的光敏剂替莫泊芬(T-SLNP),其粒径低于 50nm。我们将 T-SLNP 的功效与商业替莫泊芬制剂进行了比较,比较的方面包括在 4T1(鼠乳腺癌)和 MDA-MB-231(人乳腺癌腺癌)细胞中的体外光毒性,以及在荷 MDA-MB-231 肿瘤的 Nu/Nu 小鼠体内的抗癌效果。体外研究表明,我们的制剂设计具有更快的细胞内积累动力学,从而对肿瘤细胞产生更高的光毒性。与商业替莫泊芬制剂相比,T-SLNP 显著提高了体内抗癌效果。由于具有控制和持续释放特性、亚细胞大小、与组织和细胞的生物相容性,本研究中制备的 T-SLNP 纳米分散体代表了一种有前途的适用于癌症治疗的药物递送系统。