Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, Kraków, 30-387, Poland.
Department of Physical Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, Kraków, 30- 387, Poland.
J Nanobiotechnology. 2024 Aug 5;22(1):467. doi: 10.1186/s12951-024-02698-9.
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.
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.
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.
纳米载体的弹弹性力学性质最近被讨论为各种治疗药物有效传递的重要因素。一些数据表明，最佳纳米载体的弹性可以调节体内纳米载体的稳定性、与吞噬细胞的相互作用以及靶细胞的摄取。在这里，我们进行了一项研究，以广泛分析通过在脂质双层中形成硅酮网络来改善其弹弹性力学性质的 LIP-SS 脂质体的体内行为。我们验证了脂质体的药代动力学特征和生物分布，包括在乳腺癌小鼠模型中肿瘤的保留情况，同时在健康小鼠上分析了生物相容性。
我们表明，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、生物分布和在肿瘤中的保留情况，这表明改性的弹性没有改善纳米载体的体内性能。有趣的是，生物相容性研究表明血液形态、肝脏、脾脏和肾脏功能没有变化，但表明免疫反应的激活持续存在，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浓度增加。
将硅酮层纳入脂质体结构不会改变纳米载体在体内的特性。应该进一步修饰 LIP-SS 的表面，包括用亲水性隐形聚合物进行修饰，以显著改善其药代动力学特征和在肿瘤中的保留。LIP-SS 和 LIP-CAT 激活免疫反应导致促炎细胞因子产生增加，需要进行详细研究以阐明其机制。
