Folate-Decorated Cross-Linked Cytochrome c Nanoparticles for Active Targeting of Non-Small Cell Lung Carcinoma (NSCLC).
Folate-Decorated Cross-Linked Cytochrome c Nanoparticles for Active Targeting of Non-Small Cell Lung Carcinoma (NSCLC).
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DOI：
10.3390/pharmaceutics14030490
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发表时间：
2022-02-24
期刊：
影响因子：
5.4
通讯作者：
Griebenow KH
中科院分区：
文献类型：
--
作者：
Dominguez-Martinez I;Joaquin-Ovalle F;Ferrer-Acosta Y;Griebenow KH
叶酸受体α（FR）在包括NSCLC在内的实体瘤中过表达，可用于主动肿瘤靶向，以提供更有效的癌症治疗。在这种情况下，细胞色素c（Cyt c）引起了癌症研究的关注，因为它是无毒的，但当被递送到癌细胞的细胞质时，可以通过诱导细胞凋亡来杀死它们。采用乙腈沉淀法制备了Cyt c纳米粒（169 ± 9 nm），并通过可逆的同双功能交联进行了稳定化，实现了刺激响应释放和主动靶向相结合的基于Cyt c的给药系统。由于NPs接头中的S-S键，Cyt c在细胞内氧化还原条件下释放，而NPs在细胞外条件下保持完整而没有任何释放。NP表面装饰有亲水性叶酸-聚乙二醇（FA-PEG）聚合物，用于主动靶向。FA修饰的NP特异性识别并杀死过表达FR的癌细胞（IC 50 = 47.46 μg/mL），但对FR阴性细胞没有毒性。共聚焦显微镜证实了FR阳性癌细胞对我们的NP的优先摄取和凋亡诱导。使用刘易斯肺癌（LLC）小鼠模型的体内实验显示了可见的NP在肿瘤内的积累并抑制LLC肿瘤的生长。
The folate receptor alpha (FR), which is overexpressed in solid tumors including NSCLC, can be utilized for active tumor targeting to afford more effective cancer therapies. In this context, cytochrome c (Cyt c) has drawn attention to cancer research because it is non-toxic, yet, when delivered to the cytoplasm of cancer cells, can kill them by inducing apoptosis. Cyt c nanoparticles (NPs, 169 ± 9 nm) were obtained by solvent precipitation with acetonitrile, and stabilized by reversible homo-bifunctional crosslinking to accomplish a Cyt-c-based drug delivery system that combines stimulus-responsive release and active targeting. Cyt c was released under intracellular redox conditions, due to an S–S bond in the NPs linker, while NPs remained intact without any release under extracellular conditions. The NP surface was decorated with a hydrophilic folic acid–polyethylene glycol (FA–PEG) polymer for active targeting. The FA-decorated NPs specifically recognized and killed cancer cells (IC50 = 47.46 µg/mL) that overexpressed FR, but showed no toxicity against FR-negative cells. Confocal microscopy confirmed the preferential uptake and apoptosis induction of our NPs by FR-positive cancer cells. In vivo experiments using a Lewis lung carcinoma (LLC) mouse model showed visible NP accumulation within the tumor and inhibited the growth of LLC tumors.
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影响因子：
--
作者：
Kellar A;Egan C;Morris D
通讯作者：
Morris D
影响因子：
5.2
作者：
Barcelo-Bovea, Vanessa;Dominguez-Martinez, Irivette;Ferrer-Acosta, Yancy
通讯作者：
Ferrer-Acosta, Yancy
影响因子：
45.3
作者：
Gridelli, Cesare;Morabito, Alessandro;Perrone, Francesco
通讯作者：
Perrone, Francesco
影响因子：
8.4
作者：
Fernández M;Javaid F;Chudasama V
通讯作者：
Chudasama V
影响因子：
8
作者：
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通讯作者：
Ran H