RESULTS: We showed that fluorescently labeled LIP-SS and control LIP-CAT liposomes had similar pharmacokinetic profiles, biodistribution, and retention in tumors, indicating that modified elasticity did not improve nanocarrier in vivo performance. Interestingly, biocompatibility studies revealed no changes in blood morphology, liver, spleen, and kidney function but indicated prolonged activation of immune response manifesting in increased concentration of proinflammatory cytokines in sera of animals exposed to all tested liposomes.
CONCLUSIONS: Incorporating the silicone layer into the liposome structure did not change nanocarriers\' characteristics in vivo. Further modification of the LIP-SS surface, including decoration with hydrophilic stealth polymers, should be performed to improve their pharmacokinetics and retention in tumors significantly. Activation of the immune response by LIP-SS and LIP-CAT, resulting in elevated inflammatory cytokine production, requires detailed studies to elucidate its mechanism.
结果:我们发现荧光标记的LIP-SS和对照LIP-CAT脂质体具有相似的药代动力学特征,生物分布,保留在肿瘤中,这表明改性的弹性并没有改善纳米载体的体内性能。有趣的是,生物相容性研究显示血液形态没有变化,肝脏,脾,脾和肾功能,但表明免疫反应的激活延长,表现为暴露于所有测试脂质体的动物血清中促炎细胞因子的浓度增加。
结论:将硅酮层并入脂质体结构中不会改变纳米载体在体内的特性。LIP-SS表面的进一步改性,包括亲水隐形聚合物的装饰,应显着改善其药代动力学和在肿瘤中的保留。LIP-SS和LIP-CAT激活免疫反应,导致炎症细胞因子产生升高,需要详细的研究来阐明其机制。