Department of Chemistry, The University of Alabama in Huntsville, Huntsville, Alabama 35899, United States.
ACS Appl Bio Mater. 2023 May 15;6(5):1915-1933. doi: 10.1021/acsabm.3c00130. Epub 2023 Apr 21.
The delivery and accumulation of therapeutic drugs into cancer cells without affecting healthy cells are a major challenge for antitumor therapy. Here, we report the synthesis of a liposomal hybrid gold nano-assembly with enhanced photothermal activity for lung cancer treatment. The core components of the nano-assembly include gold nanorods coated with a mesoporous silica shell that offers an excellent drug-loading surface for encapsulation of doxorubicin. To enhance the photothermal capacity of nano-assembly, IR 780 dye was loaded inside a thermo-sensitive liposome, and then, the core nano-assembly was wrapped within the liposome, and GE-11 peptide and folic acid were conjugated onto the surface of the liposome to give the final nano-assembly [(GM@Dox) LI]-PF. The dual targeting approach of [(GM@Dox) LI]-PF leads to enhanced cellular uptake and improves the accumulation of nano-assemblies in cancer cells that overexpress the epidermal growth factor receptor and folate. The exposure of near-infrared laser irradiation can trigger photothermal-induced structural disruption of the nano-assembly, which allows for the precise and controllable release of Dox at targeted sites. Additionally, chemo-photothermal therapy was shown to be 11 times more effective in cancer cell treatment when compared to Dox alone. Our systematic study suggests that the nano-assemblies facilitate the cancer cells undergoing apoptosis via an intrinsic mitochondrial pathway that can be directly triggered by the chemo-photothermal treatment. This study offers an appealing candidate that holds great promise for synergistic cancer treatment.
将治疗药物递送到癌细胞中而不影响健康细胞是抗肿瘤治疗的一个主要挑战。在这里,我们报告了一种具有增强光热活性的脂质体杂化金纳米组装体的合成,用于肺癌治疗。该纳米组装体的核心组件包括金纳米棒,其表面涂有介孔硅壳,为封装阿霉素提供了极好的药物负载表面。为了增强纳米组装体的光热能力,IR 780 染料被装载在热敏脂质体内部,然后将核心纳米组装体包裹在脂质体内部,GE-11 肽和叶酸被共轭到脂质体表面,得到最终的纳米组装体[(GM@Dox)LI]-PF。[(GM@Dox)LI]-PF 的双重靶向方法导致细胞摄取增强,并改善了在过度表达表皮生长因子受体和叶酸的癌细胞中纳米组装体的积累。近红外激光照射的暴露可以触发纳米组装体的光热诱导结构破坏,从而允许在靶向部位精确和可控地释放 Dox。此外,与单独使用 Dox 相比,化学-光热治疗在癌症细胞治疗中显示出 11 倍的效果。我们的系统研究表明,纳米组装体通过内在的线粒体途径促进癌细胞凋亡,而这种途径可以直接被化学-光热治疗触发。这项研究提供了一种有吸引力的候选物,为协同癌症治疗带来了巨大的希望。