Rampado Riccardo, Biccari Andrea, D'Angelo Edoardo, Collino Federica, Cricrì Giulia, Caliceti Paolo, Giordano Federica, Taraballi Francesca, Pucciarelli Salvatore, Agostini Marco
Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy.
Nano-Inspired Biomedicine Lab, Institute of Pediatric Research- Città della Speranza, Padua, Italy.
Front Bioeng Biotechnol. 2022 Jun 8;10:883034. doi: 10.3389/fbioe.2022.883034. eCollection 2022.
The development of biomimetic nanoparticles (NPs) has revolutionized the concept of nanomedicine by offering a completely new set of biocompatible materials to formulate innovative drug delivery systems capable of imitating the behavior of cells. Specifically, the use of leukocyte-derived membrane proteins to functionalize nanovesicles (leukosomes) can enable their long circulation and target the inflamed endothelium present in many inflammatory pathologies and tumors, making them a promising and versatile drug delivery system. However, these studies did not elucidate the critical experimental parameters involved in leukosomes formulation. In the present study, we approached the preparation of leukosomes using a design of experiment (DoE) method to better understand the influence of experimental parameters on leukosomes features such as size, size distribution, and protein loading. We also validated this formulation technologically and tested its behavior in colorectal cancer (CRC) models, including CRC patient-derived tumor organoids (PDOs). We demonstrated leukosomes biocompatibility, endothelium adhesion capability, and tumor target in three-dimensional (3D) settings using CRC cell lines. Overall, our study offers a novel conceptual framework for biomimetic NPs using a DoE strategy and consolidates the high therapeutic potential of leukosomes as a viable drug delivery system for anti-inflammatory and antineoplastic applications.
仿生纳米颗粒（NPs）的发展彻底改变了纳米医学的概念，它提供了一套全新的生物相容性材料，用于构建能够模仿细胞行为的创新药物递送系统。具体而言，利用白细胞衍生的膜蛋白对纳米囊泡（白细胞体）进行功能化，可以使其实现长时间循环，并靶向许多炎症性疾病和肿瘤中存在的炎症内皮，使其成为一种有前景且多功能的药物递送系统。然而，这些研究并未阐明白细胞体制备过程中涉及的关键实验参数。在本研究中，我们采用实验设计（DoE）方法来制备白细胞体，以更好地理解实验参数对白细胞体特征（如大小、大小分布和蛋白质负载）的影响。我们还对该制剂进行了技术验证，并在包括结直肠癌（CRC）患者来源的肿瘤类器官（PDOs）在内的结直肠癌模型中测试了其行为。我们使用CRC细胞系在三维（3D）环境中证明了白细胞体的生物相容性、内皮粘附能力和肿瘤靶向性。总体而言，我们的研究为使用DoE策略的仿生NPs提供了一个新的概念框架，并巩固了白细胞体作为抗炎和抗肿瘤应用的可行药物递送系统的高治疗潜力。
