Ravelo-Nieto Eduardo, Cifuentes Javier, Ruiz Puentes Paola, Rueda-Gensini Laura, Quezada Valentina, Ostos Carlos, Muñoz-Camargo Carolina, Reyes Luis H, Duarte-Ruiz Alvaro, Cruz Juan C
Department of Chemistry, Universidad Nacional de Colombia, Bogotá, Colombia.
Department of Biomedical Engineering, Universidad de los Andes, Bogotá, Colombi.
Front Bioeng Biotechnol. 2023 May 9;11:1184973. doi: 10.3389/fbioe.2023.1184973. eCollection 2023.
The limited delivery of cargoes at the cellular level is a significant challenge for therapeutic strategies due to the presence of numerous biological barriers. By immobilizing the Buforin II (BUF-II) peptide and the OmpA protein on magnetite nanoparticles, a new family of cell-penetrating nanobioconjugates was developed in a previous study. We propose in this study to extend this strategy to silica nanoparticles (SNPs) and silanized fullerenol (F) as nanostructured supports for conjugating these potent cell-penetrating agents. The same molecule conjugated to distinct nanomaterials may interact with subcellular compartments differently. On the obtained nanobioconjugates (OmpA-SNPs, BUF-II-PEG-SNPs, OmpA-F, and BUF-II-PEG-F), physicochemical characterization was performed to evaluate their properties and confirm the conjugation of these translocating agents on the nanomaterials. The biocompatibility, toxicity, and internalization capacity of nanobioconjugates in Vero cells and THP-1 cells were evaluated . Nanobioconjugates had a high internalization capacity in these cells without affecting their viability, according to the findings. In addition, the nanobioconjugates exhibited negligible hemolytic activity and a low tendency to induce platelet aggregation. In addition, the nanobioconjugates exhibited distinct intracellular trafficking and endosomal escape behavior in these cell lines, indicating their potential for addressing the challenges of cytoplasmic drug delivery and the development of therapeutics for the treatment of lysosomal storage diseases. This study presents an innovative strategy for conjugating cell-penetrating agents using silica nanoparticles and silanized fullerenol as nanostructured supports, which has the potential to enhance the efficacy of cellular drug delivery.
由于存在众多生物屏障，细胞水平上货物的有限递送是治疗策略面临的重大挑战。在先前的一项研究中，通过将蟾蜍灵II（BUF-II）肽和外膜蛋白A（OmpA）固定在磁铁矿纳米颗粒上，开发了一类新的细胞穿透性纳米生物缀合物。在本研究中，我们建议将该策略扩展到二氧化硅纳米颗粒（SNP）和硅烷化富勒醇（F），作为用于缀合这些强效细胞穿透剂的纳米结构载体。与不同纳米材料缀合的同一分子可能与亚细胞区室有不同的相互作用。对获得的纳米生物缀合物（OmpA-SNP、BUF-II-PEG-SNP、OmpA-F和BUF-II-PEG-F）进行了物理化学表征，以评估它们的性质并确认这些转运剂在纳米材料上的缀合。评估了纳米生物缀合物在Vero细胞和THP-1细胞中的生物相容性、毒性和内化能力。根据研究结果，纳米生物缀合物在这些细胞中具有高内化能力，且不影响其活力。此外，纳米生物缀合物的溶血活性可忽略不计，诱导血小板聚集的倾向较低。此外，纳米生物缀合物在这些细胞系中表现出不同的细胞内运输和内体逃逸行为，表明它们有潜力应对细胞质药物递送的挑战以及开发用于治疗溶酶体贮积病的疗法。本研究提出了一种创新策略，使用二氧化硅纳米颗粒和硅烷化富勒醇作为纳米结构载体来缀合细胞穿透剂，这有可能提高细胞药物递送的功效。
