Glutathione-responsive biodegradable polyurethane nanoparticles for lung cancer treatment

JOURNAL OF CONTROLLED RELEASE

卷:321

Article

Iyer, Roshni¹  Tam Nguyen¹  Padanilam, Dona¹  Xu, Cancan¹  Saha, Debabrata³  Nguyen, Kytai T.^1,2  Hong, Yi^1,2 

[1] Univ Texas Arlington, Dept Bioengn, Arlington, TX 76019 USA

[2] Univ Texas Southwestern Med Ctr Dallas, Joint Biomed Engn Program, Dallas, TX 75390 USA

[3] Univ Texas Southwestern Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA

关键词: Glutathione;    Nanoparticles;    Lung cancer;    Cisplatin;    Stimuli responsive;   

DOI  :  10.1016/j.jconrel.2020.02.021

来源: Elsevier

【 摘 要 】

Lung cancer is one of the major causes of cancer-related deaths worldwide. Stimuli-responsive polymers and nanoparticles, which respond to exogenous or endogenous stimuli in the tumor microenvironment, have been widely investigated for spatiotemporal chemotherapeutic drug release applications for cancer chemotherapy. We developed glutathione (GSH)-responsive polyurethane nanoparticles (GPUs) using a GSH-cleavable disulfide bond containing polyurethane that responds to elevated levels of GSH within lung cancer cells. The polyurethane nanoparticles were fabricated using a single emulsion and mixed organic solvent method. Cisplatin-loaded GSH-sensitive nanoparticles (CGPU) displayed a GSH-dose dependent release of cisplatin. In addition, a significant reduction in in vitro survival fraction of A549 lung cancer cells was observed compared to free cisplatin of equivalent concentration (survival fraction of similar to psi 0.5 and similar to 0.7, respectively). The in vivo biodistribution studies showed localization of fluorescently labeled GPUs (similar to 7% of total injected dose per gram tissue) in the lung tumor regions after mouse-tail IV injections in xenograft A549 lung tumor models. The animals exposed to CGPUs also exhibited the inhibition of lung tumor growth compared to animals administered with saline (tumor growth rate of 1.5 vs. 13 in saline) and free cisplatin (tumor growth rate of 5.9) in mouse xenograft A549 lung tumor models within 14 days. These nanoparticles have potential to be used for on-demand drug release for an enhanced chemotherapy to effectively treat lung cancer.

【 授权许可】

Free