Dendron micelles have shown promising results as a multifunctional delivery system, owing to their unique molecular architecture. Herein, we have prepared a novel poly(amidoamine) (PAMAM) dendron-lipid hybrid nanoparticle (DLNP) as a nanocarrier for drug/gene co-delivery and examined how the dendron generation of DLNPs impacts their cargo-carrying capabilities. DLNPs, formed by a thin-layer hydration method, were internally loaded with chemo-drugs and externally complexed with plasmids. Compared to generation 2 dendron DLNP (D2LNPs), D3LNPs demonstrated a higher drug encapsulation efficiency (31% vs 87%) and better gene complexation (minimal N/P ratio of 20:1 vs 5:1 for complexation) due to their smaller micellar aggregation number and higher charge density, respectively. Furthermore, D3LNPs were able to avoid endocytosis and subsequent lysosomal degradation and demonstrated a higher cellular uptake than D2LNPs. As a result, D3LNPs exhibited significantly enhanced antitumor and gene transfection efficacy in comparison to D2LNPs. These findings provide design cues for engineering multifunctional dendron-based nanotherapeutic systems for effective combination cancer treatment.

中文翻译：

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用于药物/基因共递送的新型 Dendron-Lipid 纳米颗粒的尺寸依赖性载药、基因复合、细胞摄取和转染

由于其独特的分子结构，Dendron 胶束作为多功能递送系统已显示出有希望的结果。在此，我们制备了一种新型聚（酰胺胺）（PAMAM）树枝状脂质混合纳米颗粒（DLNP）作为药物/基因共递送的纳米载体，并研究了DLNPs的树枝状生成如何影响其载货能力。通过薄层水合方法形成的DLNPs内部装载有化学药物，外部与质粒复合。与第 2 代树突 DLNP (D2LNPs) 相比，D3LNPs 表现出更高的药物包封效率（31% 对 87%）和更好的基因络合（最小 N/P 比率为 20:1 对 5:1 的络合），因为它们的胶束更小聚集数和更高的电荷密度，分别。此外，D3LNPs 能够避免内吞作用和随后的溶酶体降解，并显示出比 D2LNPs 更高的细胞摄取。结果，与 D2LNPs 相比，D3LNPs 表现出显着增强的抗肿瘤和基因转染功效。这些发现为设计多功能基于树枝的纳米治疗系统提供了设计线索，以实现有效的联合癌症治疗。