3篇
您的检索式：作者名="Naroa Serna"
|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering显示文摘Modular protein engineering is suited to recruit complex and multiple functionalities in single-chain polypeptides. Although still unexplored in a systematic way, it is anticipated that the positioning of functional domains would impact and refine these activities, including the ability to organize as supramolecular entities and to generate multifunctional protein materials. To explore this concept, we have repositioned functional segments in the modular protein T22-GFP-H6 and characterized the resulting alternative fusions. In T22-GFP-H6, the combination of T22 and H6 promotes selfassembling as regular nanoparticles and selective binding and internalization of this material in CXCR4-overexpressing tumor cells, making them appealing as vehicles for selective drug delivery. The results show that the pleiotropic activities are dramatically affected in module-swapped constructs, proving the need of a carboxy terminal positioning of H6 for protein self-assembling, and the accommodation of T22 at the amino terminus as a requisite for CXCR4^+ cell binding and internalization. Furthermore, the failure of self-assembling as regular oligomers reduces cellular penetrability of the fusions while keeping the specificity of the T22-CXCR4 interaction.All these data instruct how multifunctional nanoscale protein carriers can be designed for smart, protein-driven drug delivery, not only for the treatment of CXCR4^+ human neoplasias, but also for the development of anti-HIV drugs and other pathologies in which CXCR4 is a relevant homing marker. | Eric Volta-Duran Olivia Cano-Garrido Naroa Serna Hector Lopez-Laguna Laura Sanchez-Garcia Mireia Pesarrodona Alejandro Sanchez-Chardi Ramon Mangues Antonio Villaverde Esther Vazquez Ugutz Unzueta | 2020 | Science China Materials2020，63，1： | 2 |
| 2 | 重组氯毒素构建细胞靶向的活性纳米颗粒(英文)显示文摘功能性蛋白质在纳米尺度的可控寡聚化提供了通过重组DNA技术来设计和生产改良材料和药物的可能性.氯毒素(CTX),作为一种重组的蝎毒素,由于其优先结合癌细胞的能力而引起人们的兴趣.本研究将氯毒素设计并自组装为12 nm的常规纳米颗粒,这些纳米颗粒可穿透具有和天然毒素相同受体特异性的培养细胞.这些生物相容且可生物降解的材料,表现出与同时作为载体和治疗剂的重组毒素相应的温和但仍然显著的细胞毒活性,有希望成为用于细胞靶向治疗胶质瘤的药物载体.此外,对CTX侧区域的修改可有效影响纳米颗粒的性能,说明基于CTX的构建体可通过常规基因工程来调节其多重功能性. | Raquel Díaz Laura Sánchez-García Naroa Serna Alejandro Sánchez-Chardi Olivia Cano-Garrido Julieta M.Sánchez Ugutz Unzueta Esther Vazquez Antonio Villaverde | 2019 | Science China Materials2019，62，6： | 1 |
| 3 | Self-assembling protein nanocarrier for selective delivery of cytotoxic polypeptides to CXCR4^(+) head and neck squamous cell carcinoma tumors显示文摘Loco-regional recurrences and distant metastases represent the main cause of head and neck squamous cell carcinoma(HNSCC) mortality. The overexpression of chemokine receptor 4(CXCR4) in HNSCC primary tumors associates with higher risk of developing loco-regional recurrences and distant metastases, thus making CXCR4 an ideal entry pathway for targeted drug delivery. In this context, our group has generated the self-assembling protein nanocarrier T22-GFP-H6, displaying multiple T22 peptidic ligands that specifically target CXCR4. This study aimed to validate T22-GFP-H6 as a suitable nanocarrier to selectively deliver cytotoxic agents to CXCR4^(+)tumors in a HNSCC model. Here we demonstrate that T22-GFP-H6 selectively internalizes in CXCR4^(+)HNSCC cells, achieving a high accumulation in CXCR4^(+)tumors in vivo, while showing negligible nanocarrier distribution in non-tumor bearing organs. Moreover, this T22-empowered nanocarrier can incorporate bacterial toxin domains to generate therapeutic nanotoxins that induce cell death in CXCR4-overexpressing tumors in the absence of histological alterations in normal organs. Altogether, these results show the potential use of this T22-empowered nanocarrier platform to incorporate polypeptidic domains of choice to selectively eliminate CXCR4^(+)cells in HNSCC. Remarkably, to our knowledge, this is the first study testing targeted proteinonly nanoparticles in this cancer type, which may represent a novel treatment approach for HNSCC patients. | Elisa Rioja-Blanco Irene Arroyo-Solera Patriciaálamo Isolda Casanova Alberto Gallardo Ugutz Unzueta Naroa Serna Laura Sánchez-García Miquel Quer Antonio Villaverde Esther Vázquez Ramon Mangues Lorena Alba-Castellón Xavier León | 2022 | Acta Pharmaceutica Sinica B2022，12，5： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员