开发、优化和体外评估水飞蓟宾负载聚乳酸（PLGA）纳米颗粒，并用 5TR1 Aptamer 进行装饰，用于结直肠癌细胞的靶向递送。

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-06-19 DOI:10.1208/s12249-024-02858-y

Seyyed Mobin Rahimnia, Majid Saeedi, Jafar Akbari, Katayoun Morteza-Semnani, Akbar Hedayatizadeh-Omran, Rezvan Yazdian-Robati

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引用次数: 0

摘要

化疗药物往往缺乏特异性、在肿瘤内蓄积并面临耐药性。基于纳米颗粒（NPs）的靶向给药系统可以缓解这些问题。聚（乳酸-共聚乙醇酸）（PLGA）是一种已被广泛研究的聚合物，通常用aptamers（Apts）修饰，用于癌症诊断和治疗。在本研究中，水飞蓟宾（SBN）是一种具有公认抗癌特性的天然药物，被封装到 PLGA NPs 中以控制递送并改善其溶解性差的问题。场发射扫描电子显微镜（FE-SEM）显示，SBN-PLGA NPs呈均匀的球形，直径为（138.57±1.30）nm，多分散指数（PDI）为（0.202±0.004），Zeta电位（ZP）为（-16.93±0.45）mV，包埋效率（EE）为（70.19±1.63）%。衰减全反射-傅立叶变换红外光谱（ATR-FTIR）结果表明，制剂成分之间没有化学作用，差示扫描量热法（DSC）热图证实了载体中 SBN 的有效包埋。然后，用 5TR1 Apt 对最佳配方进行功能化，以便在体外将 SBN 活性靶向递送至结直肠癌（CRC）细胞。SBN-PLGA-5TR1 纳米复合物以持续恒定的速率（零阶动力学）释放 SBN，有利于被动递送至酸性 CRC 环境。MTT 试验表明，SBN-PLGA-5TR1 纳米复合物对 C26 和 HT29 细胞的细胞毒性最高，而对正常细胞则无明显细胞毒性。细胞凋亡分析证实了这些结果，SBN-PLGA-5TR1 纳米复合物可诱导细胞早期凋亡，这表明该制剂可导致程序性死亡而非坏死。本研究首次利用 Apts 向癌细胞靶向递送 SBN。SBN-PLGA-5TR1 纳米复合物有效靶向并抑制了 CRC 细胞的增殖，为 CRC 的治疗提供了有价值的见解，同时不会对健康组织造成有害影响。

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Development, Optimization, and in vitro Evaluation of Silybin-loaded PLGA Nanoparticles and Decoration with 5TR1 Aptamer for Targeted Delivery to Colorectal Cancer Cells

Chemotherapeutic agents often lack specificity, intratumoral accumulation, and face drug resistance. Targeted drug delivery systems based on nanoparticles (NPs) mitigate these issues. Poly (lactic-co-glycolic acid) (PLGA) is a well-studied polymer, commonly modified with aptamers (Apts) for cancer diagnosis and therapy. In this study, silybin (SBN), a natural agent with established anticancer properties, was encapsulated into PLGA NPs to control delivery and improve its poor solubility. The field-emission scanning electron microscopy (FE-SEM) showed spherical and uniform morphology of optimum SBN-PLGA NPs with 138.57±1.30nm diameter, 0.202±0.004 polydispersity index (PDI), -16.93±0.45mV zeta potential (ZP), and 70.19±1.63% entrapment efficiency (EE). The results of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) showed no chemical interaction between formulation components, and differential scanning calorimetry (DSC) thermograms confirmed efficient SBN entrapment in the carrier. Then, the optimum formulation was functionalized with 5TR1 Apt for active targeted delivery of SBN to colorectal cancer (CRC) cells in vitro. The SBN-PLGA-5TR1 nanocomplex released SBN at a sustained and constant rate (zero-order kinetic), favoring passive delivery to acidic CRC environments. The MTT assay demonstrated the highest cytotoxicity of the SBN-PLGA-5TR1 nanocomplex in C26 and HT29 cells and no significant cytotoxicity in normal cells. Apoptosis analysis supported these results, showing early apoptosis induction with SBN-PLGA-5TR1 nanocomplex which indicated this agent could cause programmed death more than necrosis. This study presents the first targeted delivery of SBN to cancer cells using Apts. The SBN-PLGA-5TR1 nanocomplex effectively targeted and suppressed CRC cell proliferation, providing valuable insights into CRC treatment without harmful effects on healthy tissues.