Optimization and comparison of CD4-targeting lipid-polymer hybrid nanoparticles using different binding ligands
Optimization and comparison of CD4-targeting lipid-polymer hybrid nanoparticles using different binding ligands
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DOI：
10.1002/jbm.a.36315
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发表时间：
2018-05-01
影响因子：
4.9
通讯作者：
Woodrow, Kim A.
中科院分区：
文献类型：
--
作者：
Cao, Shijie;Jiang, Yonghou;Woodrow, Kim A.
在许多应用中，单克隆抗体和肽缀合至纳米载体（NC）的表面以用于靶向目的。然而，当与NC连接时，靶向功效可随其特异性、亲和力或亲合力而变化。NC的物理化学性质也可能影响靶向。我们比较了CD 4结合肽BP 4和抗CD 4单克隆抗体（CD 4 mAb）及其片段与脂质包被的聚（乳酸-羟基乙酸）纳米颗粒（LCNP）结合时的靶向效力。与具有DOTAP的中性或带正电荷的LCNP（dtLCNP）相比，在脂质层中具有胆固醇丁酸酯的带负电荷的LCNP（cbLCNP）显著降低非特异性结合，导致更高的靶向特异性。与CD 4抗体（CD 4-cbLCNP）或其片段（fCD 4-cbLCNP）而非BP 4缀合的cbLCNP表面显示出与人T细胞系174 xCEM的体外高结合，并且优先结合来自猪尾猕猴外周血单核细胞的CD 3 + CD 14-CD 8-细胞。CD 4-cbLCNP对CD 4 + T细胞的结合特异性比CD 8 + T细胞高10倍，而fCD 4-cbLCNP表现出最高的总体结合水平，但结合特异性仅高3倍。本研究证明了-电位对NC靶向的重要性，并表明CD 4 mAb及其片段是将治疗剂递送至CD 4 + T细胞的最佳候选物。(c)2018 Wiley Periodicals，Inc. J Biomed Mater Res Part A：106A：1177-1188，2018.
Monoclonal antibodies and peptides are conjugated to the surface of nanocarriers (NCs) for targeting purposes in numerous applications. However, targeting efficacy may vary with their specificity, affinity, or avidity when linked to NCs. The physicochemical properties of NCs may also affect targeting. We compared the targeting efficacy of the CD4 binding peptide BP4 and an anti-CD4 monoclonal antibody (CD4 mAb) and its fragments, when conjugated to lipid-coated poly(lactic-co-glycolic) acid nanoparticles (LCNPs). Negatively charged LCNPs with cholesteryl butyrate in the lipid layer (cbLCNPs) dramatically reduced nonspecific binding, leading to higher targeting specificity, compared to neutral or positively charged LCNPs with DOTAP (dtLCNP). cbLCNPs surface conjugated with a CD4 antibody (CD4-cbLCNPs) or its fragments (fCD4-cbLCNPs), but not BP4, showed high binding in vitro to the human T cell line 174xCEM, and preferential binding to CD3+ CD14-CD8- cells from pigtail macaque peripheral blood mononuclear cells. CD4-cbLCNPs showed 10-fold higher binding specificity for CD4+ than CD8+ T cells, while fCD4-cbLCNPs demonstrated the highest binding level overall, but only three-fold higher binding specificity. This study demonstrates the importance of -potential on NC targeting and indicates that CD4 mAb and its fragments are the best candidates for delivery of therapeutic agents to CD4+ T cells. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1177-1188, 2018.