Abal-Sanisidro Marcelina, Nieto-García Olaia, Cotelo-Costoya Cristina, de la Fuente María
Nano-Oncology and Translational Therapeutics group, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela (CHUS), 15706, Santiago de Compostela, Spain.
University of Santiago de Compostela (USC), 15782, Santiago de Compostela, Spain.
Chembiochem. 2024 Dec 2;25(23):e202400450. doi: 10.1002/cbic.202400450. Epub 2024 Nov 23.
Proteins are biological macromolecules well known to regulate many cellular signaling mechanisms. For instance, they are very appealing for their application as therapeutic agents, presenting high specificity and activity. Nonetheless, they suffer from unfolding, instability and low bioavailability making their administration through systemic and other routes very tough. To overcome these drawbacks, drug delivery systems and nanotechnology have arisen to deliver biomolecules in a sustained manner while, at the same time, increasing dose availability, protecting the cargo without compromising proteins' bioactivity, and enhancing intracellular delivery. In this work, we proposed the optimization of sphingomyelin nanosystems (SNs) for the delivery of a wide collection of proteins (ranging from 10-500 kDa and pI) using diverse chemical association strategies. We have further characterized SNs by varied analytical methodologies. We have also carried out in vitro experiments to validate the potential of the developed formulations. As the final goal, we aim to obtain evidence of the potential use of SNs for the development of protein therapeutics.
蛋白质是众所周知的生物大分子，可调节许多细胞信号传导机制。例如，它们作为治疗剂的应用非常具有吸引力，具有高特异性和活性。然而，它们存在展开、不稳定和生物利用度低的问题，使得通过全身和其他途径给药非常困难。为了克服这些缺点，药物递送系统和纳米技术应运而生，以持续的方式递送生物分子，同时提高剂量可用性，保护所载物而不影响蛋白质的生物活性，并增强细胞内递送。在这项工作中，我们提出了鞘磷脂纳米系统（SNs）的优化方案，以使用不同的化学结合策略递送多种蛋白质（分子量范围为10-500 kDa，且具有不同的等电点）。我们通过多种分析方法对SNs进行了进一步表征。我们还进行了体外实验，以验证所开发制剂的潜力。作为最终目标，我们旨在获得证据证明SNs在蛋白质治疗剂开发中的潜在用途。
