Nouri Faranak S, Wang Xing, Chen Xuguang, Hatefi Arash
Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.
Pharm Res. 2015 Sep;32(9):3018-28. doi: 10.1007/s11095-015-1683-5. Epub 2015 Mar 31.
One of the major hurdles facing nanomedicines is the antibody production against nanoparticles that subsequently results in their opsonization and clearance by macrophages. The objective of this research was to examine and identify the sequence of a low-immunogenic peptide based on recombinant elastin-like polypeptides (ELPs) that does not evoke IgG response and can potentially be used for masking the surfaces of the nanoparticles.
Biopolymers composed of a DNA condensing domain in fusion with anionic, neutral and cationic elastin-like peptides were genetically engineered. The biopolymers were used to complex with plasmid DNA and form ELP-coated nanoparticles. Then, the potential immunogenicity of nanoparticles in terms of IgM/IgG response after repeated injections was evaluated in Balb/c immunocompetent mice.
The results revealed the sequence of a non-immunogenic ELP construct that in comparison to control group did not elicit any significant IgG response, whereas the vector/DNA complexes that were coated with polyethylene glycol (PEG) did elicit significant IgG response under the same conditions.
The identification of the sequence of an ELP-based peptide that does not induce IgG response opens the door to more focused in-depth immunotoxicological studies which could ultimately lead to the production of safer and more effective drug/gene delivery systems such as liposomes, micelles, polymeric nanoparticles, viruses and antibodies.
纳米药物面临的主要障碍之一是针对纳米颗粒产生抗体，这随后会导致其被巨噬细胞调理吞噬并清除。本研究的目的是研究和鉴定一种基于重组弹性蛋白样多肽（ELP）的低免疫原性肽的序列，该序列不会引发IgG反应，并有可能用于掩盖纳米颗粒的表面。
对由与阴离子、中性和阳离子弹性蛋白样肽融合的DNA凝聚结构域组成的生物聚合物进行基因工程改造。这些生物聚合物用于与质粒DNA复合，形成ELP包被的纳米颗粒。然后，在Balb/c免疫活性小鼠中评估重复注射后纳米颗粒在IgM/IgG反应方面的潜在免疫原性。
结果揭示了一种非免疫原性ELP构建体的序列，与对照组相比，该序列未引发任何显著的IgG反应，而在相同条件下，用聚乙二醇（PEG）包被的载体/DNA复合物确实引发了显著的IgG反应。
鉴定出不诱导IgG反应的基于ELP的肽序列，为更有针对性的深入免疫毒理学研究打开了大门，最终可能导致生产更安全、更有效的药物/基因递送系统，如脂质体、胶束、聚合物纳米颗粒、病毒和抗体。
