PDF(Pubmed)
Abstract：
Functional polymer-lipid hybrid nanoparticles (H-NPs) are a promising class of nanocarriers that combine the benefits of polymer and lipid nanoparticles, offering biocompatibility, structural stability, high loading capacity, and, most importantly, superior surface functionalization. Here, we report the synthesis and design of highly functional H-NPs with specificity toward the transferrin receptor (TfR), using a small molecule ligand, gambogic acid (GA). A fluorescence study revealed the molecular orientation of H-NPs, where the lipid-dense core is surrounded by a polymer exterior, functionalized with GA. Urolithin A, an immunomodulator and anti-inflammatory agent, served as a model drug-like compound to prepare H-NPs via traditional emulsion-based techniques, where H-NPs led to smaller particles (132 nm) and superior entrapment efficiencies (70 % at 10 % drug loading) compared to GA-conjugated polymeric nanoparticles (P-NPs) (157 nm and 52 % entrapment efficiency) and solid lipid nanoparticles (L-NPs) (186 nm and 29 % entrapment efficiency). H-NPs showed superior intracellular accumulation compared to individual NPs using human small intestinal epithelial (FHs 74) cells. The in vitro efficacy was demonstrated by flow cytometry analysis, in which UA-laden H-NPs showed excellent anti-inflammatory properties in cisplatin-induced injury in healthy human proximal tubular cell (HK2) model by decreasing the TLR4, NF-κβ, and IL-β expression. This preliminary work highlights the potential of H-NPs as a novel functional polymer-lipid drug delivery system, establishing the foundation for future research on its therapeutic potential in addressing chemotherapy-induced acute kidney injury in cancer patients.
摘要：
功能性聚合物-脂质混合纳米颗粒（H-NP）是一类有前途的纳米载体，结合了聚合物和脂质纳米颗粒的好处，提供生物相容性，结构稳定性,高承载能力，and,最重要的是,优越的表面功能化。这里,我们报道了对转铁蛋白受体（TfR）具有特异性的高功能H-NP的合成和设计，使用小分子配体，藤黄酸（GA）。荧光研究揭示了H-NP的分子取向，脂质致密的核心被聚合物包围，用GA功能化。尿磷脂A,免疫调节剂和抗炎剂，作为通过传统的基于乳液的技术制备H-NP的模型药物样化合物，其中与GA缀合的聚合物纳米颗粒（P-NP）（157nm和52％的包封效率）和固体脂质纳米颗粒（L-NP）（186nm和29％的包封效率）相比，H-NP导致更小的颗粒（132nm）和更高的包封效率（10％的载药量为70％）。与使用人小肠上皮(FHs74)细胞的单个NP相比,H-NP显示出优异的细胞内积累。通过流式细胞术分析证明了体外功效，其中，在顺铂诱导的健康人近端肾小管细胞（HK2）模型中，通过降低TLR4，NF-κβ，和IL-β表达。这项初步工作强调了H-NP作为新型功能性聚合物-脂质药物递送系统的潜力，为未来研究其在解决癌症患者化疗引起的急性肾损伤方面的治疗潜力奠定了基础。
