Department of Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy.
Department of Pure and Applied Sciences, Università degli studi di Urbino "Carlo Bo", Urbino 61029, Italy.
Nanoscale. 2022 Mar 24;14(12):4654-4670. doi: 10.1039/d1nr06583a.
Anti-(ds)-DNA antibodies are the serological hallmark of Systemic Lupus Erythematosus (SLE). They assemble in the bloodstream with (ds)-DNA, forming immunocomplexes, which spread all over the body causing, among the other symptoms, lupic glomerulonephritis. Pathological manifestations of the disease may be reduced by destabilizing or inhibiting the formation of the immunocomplexes. In this respect, glycodendrimers showed peculiar interacting abilities towards this kind of biomolecule. Various generations of open-shell maltose-decorated poly(amidoamine) (PAMAM) and poly(propyleneimine) (PPI) dendrimers and two oligopeptides with different polyethylene glycol units were synthesized and characterized, and then tested for their anti-SLE activity. The activity of glycodendrimers and oligopeptides was evaluated in human plasma from patients with SLE, compared to healthy plasma, by means of an enzyme-linked immunosorbent assay (ELISA), and electron paramagnetic resonance (EPR) characterization using spin-label and spin-probe techniques. Different strategies for the immunocomplex formation were tested. The results show that both kinds of glycodendrimers and oligopeptides inhibited the formation of immunocomplexes. Also, a partial breakdown of preformed immunocomplexes was observed. Both ELISA and EPR analyses indicated a better activity of glycodendrimers compared to oligopeptides, the 3 generation PPI dendrimer being the most promising against SLE. This study highlights the possibility to develop a new class of dendritic therapeutics for the treatment of Lupus in pre-clinical studies.
抗双链 DNA 抗体是系统性红斑狼疮 (SLE) 的血清学标志。它们与双链 DNA 在血液中组装，形成免疫复合物，这些复合物会在全身扩散，导致狼疮性肾炎等症状。通过破坏或抑制免疫复合物的形成，可以减轻疾病的病理表现。在这方面，糖基化树枝状聚合物对这种生物分子具有独特的相互作用能力。合成并表征了各种代数的开壳麦芽糖修饰的聚(酰胺-胺) (PAMAM) 和聚(丙烯亚胺) (PPI) 树枝状聚合物以及两种具有不同聚乙二醇单元的寡肽，然后对其抗 SLE 活性进行了测试。通过酶联免疫吸附试验 (ELISA)，并使用自旋标记和自旋探针技术的电子顺磁共振 (EPR) 表征，在来自 SLE 患者的人血浆中以及在健康血浆中评估了糖基化树枝状聚合物和寡肽的活性。测试了不同的免疫复合物形成策略。结果表明，两种类型的糖基化树枝状聚合物和寡肽都抑制了免疫复合物的形成。此外，还观察到预形成的免疫复合物的部分分解。ELISA 和 EPR 分析均表明，与寡肽相比，糖基化树枝状聚合物具有更好的活性，其中第 3 代 PPI 树枝状聚合物对 SLE 的治疗最有希望。这项研究强调了在临床前研究中开发治疗狼疮的新型树枝状治疗药物的可能性。
