PDF(Pubmed)
Abstract：
BACKGROUND: The elastomechanical properties of nanocarriers have recently been discussed as important for the efficient delivery of various therapeutics. Some data indicate that optimal nanocarriers\' elasticity can modulate in vivo nanocarrier stability, interaction with phagocytes, and uptake by target cells. Here, we presented a study to extensively analyze the in vivo behavior of LIP-SS liposomes that were modified by forming the silicone network within the lipid bilayers to improve their elastomechanical properties. We verified liposome pharmacokinetic profiles and biodistribution, including retention in tumors on a mouse model of breast cancer, while biocompatibility was analyzed on healthy mice.
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.
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.
摘要：
背景:最近已经讨论了纳米载体的弹性力学性质对于有效递送各种治疗剂是重要的。一些数据表明，最佳的纳米载体弹性可以调节体内纳米载体的稳定性，与吞噬细胞相互作用，和靶细胞的摄取。这里,我们提出了一项研究，以广泛分析LIP-SS脂质体的体内行为，这些脂质体通过在脂质双层内形成硅酮网络以改善其弹性力学性能而被修饰。我们验证了脂质体的药代动力学和生物分布，包括保留在乳腺癌小鼠模型的肿瘤中，而对健康小鼠的生物相容性进行了分析。
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。
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。
