Tian Jing, Min Yuanzeng, Rodgers Zachary, Au Kin Man, Hagan C Tilden, Zhang Maofan, Roche Kyle, Yang Feifei, Wagner Kyle, Wang Andrew Z
School of Biological and Environmental Engineering, Tianjin Vocational Institute, Tianjin 300410, P. R. China.
Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Mater Chem B. 2017 Aug 14;5(30):6049-6057. doi: 10.1039/C7TB01370A. Epub 2017 Jul 5.
Chemoradiotherapy (CRT) with paclitaxel (PTX) and cisplatin (CP) is part of the standard of care for patients with locally advanced non-small cell lung cancer (NSCLC). Despite the high treatment intensity, many patients still develop local recurrence after treatment. Thus, there is a strong need to further improve CRT for lung cancer. One strategy is to co-deliver cytotoxic chemotherapy agents using biocompatible nanoparticles (NPs) which can limit off-target tissue toxicity and improve therapeutic efficacy. Herein, we report the development of dual-drug loaded nanoformulations that improve the efficacy of CRT for NSCLC by co-encapsulation of cisplatin (CP) and PTX in PLGA-PEG NPs. Mice bearing NSCLC xenografts given the dual-drug loaded NPs during CRT showed greater inhibition of tumor growth than free drug combinations or combinations of single-drug loaded NPs. These results indicate that using a NP co-delivery strategy for this common CRT regimen may improve clinical responses in NSCLC patients.
采用紫杉醇(PTX)和顺铂(CP)的放化疗(CRT)是局部晚期非小细胞肺癌(NSCLC)患者标准治疗方案的一部分。尽管治疗强度很高,但许多患者在治疗后仍会出现局部复发。因此,迫切需要进一步改进肺癌的CRT。一种策略是使用生物相容性纳米颗粒(NP)共同递送细胞毒性化疗药物,这可以限制脱靶组织毒性并提高治疗效果。在此,我们报告了双药负载纳米制剂的研发,该制剂通过将顺铂(CP)和PTX共包封在PLGA-PEG NPs中提高了NSCLC的CRT疗效。在CRT期间给予双药负载NP的携带NSCLC异种移植瘤的小鼠,其肿瘤生长抑制作用比游离药物组合或单药负载NP的组合更强。这些结果表明,对这种常见的CRT方案采用NP共递送策略可能会改善NSCLC患者的临床反应。