基于核酸 (NA) 的疗法通过其在基因水平上控制细胞功能的能力正在彻底改变生物医学研究。这项工作展示了一种多功能的弹性蛋白样多肽 (ELP) 载体系统，采用逐层 (LbL) 配方方法，可输送大小从 siRNA 到质粒的 NA 货物。该系统的组件可以重新配置，以调节载体的生化和生物物理特性，以接合生物靶标的独特特征。我们展示了 LbL ELP 核酸纳米颗粒 (LENN) 在小鼠和人类膀胱肿瘤细胞系中的物理特征和生物学性能。由于尿液不断流入膀胱，导致膀胱内滴注治疗药物的接触时间短（通常<2小时），因此靶向膀胱肿瘤很困难。 LENN 复合物在 30 分钟内与膀胱肿瘤细胞结合，并在 60 分钟内快速内化以释放其 NA 货物。我们的数据表明，已经创建了一种易于适应的 NA 输送系统，其目标能力、货物尺寸和拆卸动力学都很灵活。这种方法为脂质纳米颗粒制剂（效率低下和物理化学不稳定）或病毒载体（受制造和免疫排斥挑战困扰）提供了一条替代途径。这种基于 ELP 的敏捷纳米载体提供了一种核酸递送的替代途径，使用可生物制造、可生物降解、生物相容性和高度可调的载体，能够通过与过表达的细胞表面受体结合来靶向细胞。

Nucleic acid (NA)-based therapies are revolutionizing biomedical research through their ability to control cellular functions at the genetic level. This work demonstrates a versatile elastin-like polypeptide (ELP) carrier system using a layer-by-layer (LbL) formulation approach that delivers NA cargos ranging in size from siRNA to plasmids. The components of the system can be reconfigured to modulate the biochemical and biophysical characteristics of the carrier for engaging the unique features of the biological target. We show the physical characterization and biological performance of LbL ELP nucleic acid nanoparticles (LENNs) in murine and human bladder tumor cell lines. Targeting bladder tumors is difficult owing to the constant influx of urine into the bladder, leading to low contact times (typically <2 h) for therapeutic agents delivered via intravesical instillation. LENN complexes bind to bladder tumor cells within 30 min and become rapidly internalized to release their NA cargo within 60 min. Our data show that a readily adaptable NA-delivery system has been created that is flexible in its targeting ability, cargo size, and disassembly kinetics. This approach provides an alternative path to either lipid nanoparticle formulations that suffer from inefficiency and physicochemical instability or viral vectors that are plagued by manufacturing and immune rejection challenges. This agile ELP-based nanocarrier provides an alternative route for nucleic acid delivery using a biomanufacturable, biodegradable, biocompatible, and highly tunable vehicle capable of targeting cells via engagement with overexpressed cell surface receptors.