硼苯丙氨酸修饰的聚多巴胺纳米颗粒用于达沙替尼在非小细胞肺癌中的靶向递送
Boron Phenylalanine-Modified Polydopamine Nanoparticles for Targeted Delivery of Danusertib in Non-Small Cell Lung Cancer.
作者信息
Xu Yi, Chen Xiang, Zhang Lin, Li Ping, He Jiahuan, Zhu Meiyu, Makvandi Pooyan, Jin Xuru
机构信息
Department of Urology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, People's Republic of China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
出版信息
Int J Nanomedicine. 2025 Jun 28;20:8415-8432. doi: 10.2147/IJN.S519608. eCollection 2025.
PURPOSE
Aurora-A is often overexpressed in lung cancer and is associated with poor prognosis, making it a potential therapeutic target for non-small cell lung cancer (NSCLC) treatment. This study aimed to evaluate the therapeutic potential of nanomedicine-based delivery of the Aurora-A inhibitor Danusertib (Danu) in NSCLC treatment.
METHODS
Boron phenylalanine (BPA)-modified polydopamine (PDA) was used as a carrier to load Danu, preparing B-PDA@Danu nanoparticles. The structure, microstructure, particle size, zeta potential, stability, drug loading capacity, loading rate, and in vitro release were characterized. In vitro studies investigated its effects on A549 cell viability, apoptosis, uptake ability, and cell cycle. In vivo studies examined its distribution and/or anti-tumor effects in subcutaneous xenograft tumors in mice. The anti-tumor effects and biosafety of B-PDA@Danu were studied in a subcutaneous xenograft tumor model in mice. The in vivo distribution and anti-tumor effects of B-PDA@Danu were studied in a mouse lung carcinoma in situ model.
RESULTS
The synthesized B-PDA@Danu nanoparticles were spherical, negatively charged, with an average particle size of (172.96±1.61) nm, exhibited good stability, and efficiently loaded Danu. B-PDA@Danu promoted cellular uptake in vitro, inhibited cell viability (P < 0.001), induced G2/M cell cycle arrest (P < 0.001), and increased apoptosis (P < 0.001). In the subcutaneous xenograft tumor model, B-PDA@Danu suppressed tumor growth (P < 0.001), induced cell cycle arrest in tumor cells (P < 0.001), caused tumor tissue damage, and showed good biosafety. In the mouse lung carcinoma in situ model, B-PDA@Danu effectively targeted and accumulated at the site of carcinogenesis, leading to tumor shrinkage.
CONCLUSION
B-PDA@Danu provides a novel nanomedicine approach for anti-NSCLC therapy that enables targeted tumor elimination with low potential toxicity.
目的
极光激酶A（Aurora-A）在肺癌中常过度表达，且与预后不良相关，这使其成为非小细胞肺癌（NSCLC）治疗的潜在靶点。本研究旨在评估基于纳米药物递送极光激酶A抑制剂达努西布（Danu）在NSCLC治疗中的治疗潜力。
方法
以硼苯丙氨酸（BPA）修饰的聚多巴胺（PDA）为载体负载Danu，制备B-PDA@Danu纳米颗粒。对其结构、微观结构、粒径、zeta电位、稳定性、载药量、装载率及体外释放进行表征。体外研究考察其对A549细胞活力、凋亡、摄取能力及细胞周期的影响。体内研究检测其在小鼠皮下异种移植瘤中的分布和/或抗肿瘤作用。在小鼠皮下异种移植瘤模型中研究B-PDA@Danu的抗肿瘤作用和生物安全性。在小鼠原位肺癌模型中研究B-PDA@Danu的体内分布和抗肿瘤作用。
结果
合成的B-PDA@Danu纳米颗粒呈球形，带负电荷，平均粒径为（172.96±1.61）nm，稳定性良好，能有效负载Danu。B-PDA@Danu在体外促进细胞摄取，抑制细胞活力（P<0.001），诱导G2/M期细胞周期阻滞（P<0.001），并增加凋亡（P<0.001）。在皮下异种移植瘤模型中，B-PDA@Danu抑制肿瘤生长（P<0.001），诱导肿瘤细胞周期阻滞（P<0.001），造成肿瘤组织损伤，且具有良好的生物安全性。在小鼠原位肺癌模型中，B-PDA@Danu有效靶向并聚集在肿瘤发生部位，导致肿瘤缩小。
结论
B-PDA@Danu为抗NSCLC治疗提供了一种新型纳米药物方法，能够以低潜在毒性实现靶向肿瘤清除。
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