Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Shanghai, 200032, China.
J Mater Chem B. 2020 Jan 28;8(4):655-665. doi: 10.1039/c9tb02284h. Epub 2020 Jan 6.
Stimuli response or controlled release is a new research hotspot in nanomedicine; however, there is scarce research on organic nanomedicines with stimuli responses, which limits their practical biological applications. In addition, homoharringtonine (HHT) has been used as an effective anticancer agent, but reducing its toxicity and side effects is an urgent problem to be solved. Herein, an EGFR (epidermal growth factor receptor) aptamer-modified HHT-loaded PLGA-SS-PEG nanomedicine was developed. The nanomaterial possesses spherical morphology and admirable biocompatibility. After targeted endocytosis in tumour cells via the selective recognition between EGFR and its aptamer, the PLGA nanomedicine is triggered by a high GSH level and releases its cargo in lung cancer cells. The in vitro and in vivo results reveal that the PLGA nanomedicine not only inhibited the proliferation and promoted the apoptosis of lung cancer cells, but also possessed better therapeutic efficacy and less toxic side effects compared with the free anticancer agent. Consequently, this study provides a novel approach to construct a biodegradable nanomedicine with targeted recognition and stimuli response. Moreover, it inhibited the proliferation of lung cancer cells with high efficiency and low toxicity. Importantly, the PLGA nanomedicine demonstrates encouraging potential as a multifunctional nano-system applicable for cancer therapy.
刺激响应或控制释放是纳米医学的一个新的研究热点;然而,具有刺激响应的有机纳米药物的研究却很少,这限制了它们在实际生物应用中的发展。此外,高三尖杉酯碱(HHT)已被用作有效的抗癌药物,但降低其毒性和副作用是一个亟待解决的问题。在此,我们开发了一种表皮生长因子受体(EGFR)适体修饰的载高三尖杉酯碱的 PLGA-SS-PEG 纳米药物。该纳米材料具有球形形态和良好的生物相容性。在通过 EGFR 与其适体的选择性识别,靶向内化进入肿瘤细胞后,PLGA 纳米药物在高 GSH 水平下被触发,并在肺癌细胞中释放其载药。体外和体内结果表明,与游离抗癌药物相比,PLGA 纳米药物不仅抑制了肺癌细胞的增殖并促进了其凋亡,而且还具有更好的治疗效果和更少的毒副作用。因此,本研究为构建具有靶向识别和刺激响应的可生物降解纳米药物提供了一种新方法。此外,该纳米药物高效低毒地抑制了肺癌细胞的增殖。重要的是,PLGA 纳米药物作为一种多功能的癌症治疗用纳米系统具有令人鼓舞的应用潜力。