■分子靶向治疗是非小细胞肺癌最关键的治疗策略之一,然而,其疗效因水溶性差而严重受损,低生物利用度和肿瘤积累不足的靶向药物。为了提高靶向药物的疗效,我们展示了一种基于厄洛替尼的新型自组装两亲性分子作为抗癌治疗的有效纳米药物.
■合成了由疏水性埃罗替尼和亲水性生物素嵌段组成的两亲性分子,并通过核磁共振(NMR)以及高分辨率质谱(HRMS)进行了表征。然后,两亲性分子的纳米组装体通过使用纳米沉淀法进行配制。随后,尺寸,形态学,细胞摄取,通过一些方法系统地评估了新构建的埃罗替尼纳米药物的抗癌活性和体内分布,包括透射电子显微镜(TEM),动态光散射(DLS),流式细胞术,体内成像系统等.
■我们开发了一种新型的厄洛替尼纳米制剂,其具有45%的高载药量。具有结构明确、体积小等特点,获得的纳米药物可以有效地积累在肿瘤部位,并被癌细胞迅速内化。最后,与游离埃罗替尼相比,基于埃罗替尼的纳米制剂在体外和体内均显示出明显更好的抗癌活性.此外,纳米药物显示出很大的耐受性。
■结合纳米技术和自组装的优点,这种新型的厄洛替尼纳米药物是癌症治疗的有希望的候选治疗药物.这项研究还强调了两亲性分子在提高药物疗效和降低药物毒性方面的潜在用途。这可能成为制备活性剂纳米药物的一般策略。
UNASSIGNED: Molecular targeted therapy is one of the most pivotal strategies in the treatment of non-small cell lung cancer, yet its curative effect is severely compromised by the poor aqueous solubility, low bioavailability and inadequate tumor accumulation of targeted agents. To enhance the efficacy of targeted agents, we demonstrate a novel self-assemble amphiphilic molecule based on erlotinib as an effective nanodrug for anti-cancer treatment.
UNASSIGNED: An amphiphilic molecule composed of hydrophobic erlotinib and hydrophilic biotin block was synthesized and characterized by nuclear magnetic resonance (NMR) as well as high-resolution mass spectrometry (HRMS). Then, nanoassemblies of the amphiphilic molecules are formulated by using nanoprecipitation method. Subsequently, the size, morphology, cell uptake, the anticancer activity and in vivo distribution of the newly constructed erlotinib nanodrug were systematically assessed by some methods, including transmission electron microscopy (TEM), dynamic light-scattering (DLS), flow cytometry, in vivo imaging system etc.
UNASSIGNED: We developed a novel nanoformulation of erlotinib, which possesses a high drug loading of 45%. With the features of well-defined structure and small size, the obtained nanodrug could be effectively accumulated in tumor sites and rapidly internalized by cancer cells. Finally, the erlotinib-based nanoformulation showed considerably better anticancer activity compared to free erlotinib both in vitro and in vivo. Moreover, the nanodrug displayed great tolerability.
UNASSIGNED: Combining the advantageous features of both nanotechnology and self-assemble, this novel erlotinib nanomedicine constitutes a promising therapeutic candidate for cancer treatment. This study also underlines the potential use of amphiphilic molecule for improving drug efficacy as well as reducing drug toxicity, which could become a general strategy for the preparation of nanodrugs of active agents.