Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi 221005, UP, India.
PK-PD Tox & Formulation Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India.
Int J Biol Macromol. 2022 Nov 30;221:874-890. doi: 10.1016/j.ijbiomac.2022.09.053. Epub 2022 Sep 9.
Cabazitaxel (CZT) loaded chitosan-alginate based (CSA) nanoparticles were developed with dual targeting functions of both folate receptor and epidermal growth factor receptor (EGFR) using ionic gelation technique. The chitosan-folate conjugate was synthesized, and characterized by using FTIR, NMR and Mass spectroscopy. The physicochemical parameters and morphology of all CSA nanoparticles were examined. The degree of conjugation of folic acid and cetuximab (CTXmab) was determined by UV-Visible spectroscopy and Bradford assay, respectively. Moreover, XPS analysis also supported the presence of the ligands on nanoparticles. The cellular-uptake study performed on A-549 cells demonstrated a significant enhancement in the uptake of dual-receptor targeted CSA nanoparticles than non-targeted and single-receptor targeted CSA nanoparticles. Further, CZT-loaded dual receptors targeted CSA nanoparticles also showed significantly lower IC values (~38 folds) than the CZT control against A-549 cells. Further, in-vivo histopathological evaluations of dual receptor-targeted CSA nanoparticles have demonstrated better safety in Wistar rats. Moreover, its treatment on the Benzo(a)pyrene (B(a)P) induced lung cancer mice model has showed the enhanced anticancer efficacy of CZT with a prolonged survival rate.
载紫杉醇（CZT）的壳聚糖-海藻酸钠（CSA）纳米粒通过离子凝胶技术被开发出了叶酸受体和表皮生长因子受体（EGFR）的双重靶向功能。壳聚糖-叶酸偶联物通过傅里叶变换红外光谱（FTIR）、核磁共振（NMR）和质谱（Mass spectroscopy）进行了合成和表征。所有 CSA 纳米粒的理化参数和形态都进行了检测。通过紫外可见分光光度法（UV-Visible spectroscopy）和 Bradford assay 分别测定了叶酸和西妥昔单抗（CTXmab）的偶联度。此外，X 射线光电子能谱（XPS）分析也支持配体存在于纳米粒上。在 A-549 细胞上进行的细胞摄取研究表明，与非靶向和单受体靶向 CSA 纳米粒相比，双重受体靶向 CSA 纳米粒的摄取显著增强。此外，载 CZT 的双重受体靶向 CSA 纳米粒对 A-549 细胞的 IC 值（~38 倍）也显著低于 CZT 对照。进一步，对 Wistar 大鼠的体内组织病理学评估表明，双重受体靶向 CSA 纳米粒具有更好的安全性。此外，其对苯并（a）芘（B(a)P）诱导的肺癌小鼠模型的治疗表明，CZT 的抗癌疗效增强，存活率延长。
