化学
细胞毒性
叶酸受体
A549电池
生物物理学
表皮生长因子受体
壳聚糖
纳米颗粒
药物输送
体外
癌细胞
受体
生物化学
纳米技术
材料科学
癌症
有机化学
生物
医学
内科学
作者
Vikas Vikas,Abhishesh Kumar Mehata,Matte Kasi Viswanadh,Ankit Kumar Malik,Aseem Setia,Pooja Kumari,Sanjeev Kumar Mahto,Madaswamy S. Muthu
出处
期刊:Biomacromolecules
[American Chemical Society]
日期:2023-10-23
卷期号:24 (11): 4989-5003
被引量:23
标识
DOI:10.1021/acs.biomac.3c00658
摘要
In this research, we have modified tocopheryl polyethylene glycol succinate (TPGS) to a redox-sensitive material, denoted as TPGS-SH, and employed the same to develop dual-receptor-targeted nanoparticles of chitosan loaded with cabazitaxel (CZT). The physicochemical properties and morphological characteristics of all nanoparticle formulations were assessed. Dual-receptor targeting redox-sensitive nanoparticles of CZT (F-CTX-CZT-CS-SH-NPs) were developed by a combination of pre- and postconjugation techniques by incorporating synthesized chitosan-folate (F) and TPGS-SH during nanoparticle synthesis and further postconjugated with cetuximab (CTX) for epidermal growth factor receptor (EGFR) targeting. The in vitro release of the drug was seemingly higher in the redox-sensitive buffer media (GSH, 20 mM) compared to that in physiological buffer. However, the extent of cellular uptake of dual-targeted nanoparticles was significantly higher in A549 cells than other control nanoparticles. The IC50 values of F-CTX-CZT-CS-SH-NPs against A549 cells was 0.26 ± 0.12 μg/mL, indicating a 6.3-fold and 60-fold enhancement in cytotoxicity relative to that of dual-receptor targeted, nonredox sensitive nanoparticles and CZT clinical injection, respectively. Furthermore, F-CTX-CZT-CS-SH-NPs demonstrated improved anticancer activity in the benzo(a)pyrene lung cancer model with a higher survival rate. Due to the synergistic combination of enhanced permeability and retention (EPR) effect of small-sized nanoparticles, the innovative and redox sensitive TPGS-SH moiety and the dual folate and EGFR mediated augmented endocytosis have all together significantly enhanced their biodistribution and targeting exclusively to the lung which is evident from their ultrasound/photoacoustic and in vivo imaging system (IVIS) studies.
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