Engineering the lipid layer of lipid-PLGA hybrid nanoparticles for enhanced in vitro cellular uptake and improved stability
Engineering the lipid layer of lipid-PLGA hybrid nanoparticles for enhanced in vitro cellular uptake and improved stability
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DOI：
10.1016/j.actbio.2015.09.032
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发表时间：
2015-12-01
影响因子：
9.7
通讯作者：
Zhang, Chenming
中科院分区：
文献类型：
--
作者：
Hu, Yun;Hoerle, Reece;Zhang, Chenming
脂质-聚合物混合纳米颗粒 (NP) 由聚合物核心和脂质壳组成，作为癌症药物、显像剂和疫苗的输送系统已得到深入研究。特别是对于疫苗应用，杂化纳米粒子需要能够在循环过程中保护封闭的抗原，易于被树突状细胞摄取，并具有良好的长期储存稳定性。然而，脂质成分对杂化纳米粒子性能的影响尚未得到充分研究。在这项研究中，我们证明，脂质层中胆固醇浓度越高，人血清和磷酸盐缓冲盐水 (PBS) 中的脂质聚丙交酯乙交酯酸 (脂质-PLGA) 纳米粒子的抗原释放速度就越慢且更受控制。较高浓度的胆固醇还促进杂化纳米颗粒的体外细胞摄取，提高脂质层的稳定性，并在长期储存期间保护杂化结构的完整性。然而，高胆固醇含量的稳定杂化结构在储存过程中往往会相互融合，导致尺寸显着增加并降低细胞摄取。其他实验表明，纳米粒子的聚乙二醇化可以有效地最大限度地减少长期储存后融合引起的尺寸增加，从而改善细胞摄取，尽管过度的聚乙二醇化不会有益并导致改善程度降低。意义声明本文报道了包裹聚合物纳米颗粒的脂质层的工程设计，该聚合物纳米颗粒可用作药物和疫苗分子的载体进行靶向递送。我们证明，胆固醇的浓度对于树突状细胞（传递免疫效应分子的靶细胞）的稳定性和摄取混合纳米颗粒至关重要。然而，我们发现具有高胆固醇浓度的混合纳米颗粒在储存过程中往往会融合，导致颗粒较大，细胞摄取减少。随后通过对混合纳米颗粒进行聚乙二醇化解决了这个问题。随着脂质聚合物杂化纳米粒子在药物和疫苗递送中的研究和临床应用的增加，这项工作将显着影响杂化纳米粒子的设计，以最大限度地减少循环过程中的分子释放并提高目标分子的生物利用度。 (C) 2015 Acta Materialia Inc. 由 Elsevier Ltd 出版。保留所有权利。
Lipid-polymer hybrid nanoparticles (NPs), consisting of a polymeric core and a lipid shell, have been intensively examined as delivery systems for cancer drugs, imaging agents, and vaccines. For applications in vaccine particularly, the hybrid NPs need to be able to protect the enclosed antigens during circulation, easily be up-taken by dendritic cells, and possess good stability for prolonged storage. However, the influence of lipid composition on the performance of hybrid NPs has not been well studied. In this study, we demonstrate that higher concentrations of cholesterol in the lipid layer enable slower and more controlled antigen release from lipid-poly(lactide-co-glycolide) acid (lipid-PLGA) NPs in human serum and phosphate buffered saline (PBS). Higher concentrations of cholesterol also promoted in vitro cellular uptake of hybrid NPs, improved the stability of the lipid layer, and protected the integrity of the hybrid structure during long-term storage. However, stabilized hybrid structures of high cholesterol content tended to fuse with each other during storage, resulting in significant size increase and lowered cellular uptake. Additional experiments demonstrated that PEGylation of NPs could effectively minimize fusion-caused size increase after long term storage, leading to improved cellular uptake, although excessive PEGylation will not be beneficial and led to reduced improvement.Statement of SignificanceThis paper reports the engineering of the lipid layer that encloses a polymeric nanoparticle, which can be used as a carrier for drug and vaccine molecules for targeted delivery. We demonstrated that the concentration of cholesterol is critical for the stability and uptake of the hybrid nanoparticles by dendritic cells, a targeted cell for the delivery of immune effector molecules. However, we found that hybrid nanoparticles with high cholesterol concentration tend to fuse during storage resulting in larger particles with decreased cellular uptake. This problem is subsequently solved by PEGylating the hybrid nanoparticles. With increased research and clinical applications of lipid-polymer hybrid nanoparticles in drug and vaccine delivery, this work will significantly impact the design of the hybrid nanoparticles for minimized molecule release during circulation and increased bioavailability of the target molecules. (C) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.