Liu Yan, Tian Jia, Fu Yulei, Yang Yingjie, Chen Mingmao, Zhang Qiqing
CAS Key Laboratory of Design and Assembly of Functional Nanostructures, and Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.
Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002, China.
Biomater Sci. 2021 Feb 9;9(3):700-711. doi: 10.1039/d0bm01748e.
Currently, the in situ on/off switch of PTT/PDT reagents for tumor treatment has evoked considerable interest in the field of cancer therapy. However, the actual PTT/PDT therapy efficacy in tumor treatment is largely restricted by the PTT/PDT reagents' aggregation issues during their release from the hydrophobic carrier to the hydrophilic tumor microenvironment. Thus, it remains a challenge to break through the therapy barrier caused by the PTT/PDT agent aggregation and achieve substantial improvement of anticancer efficacy. In this work, we developed a novel near-infrared (NIR) light-responsive and gas bubble-generated liposomal nanobomb (Cy/Ce6/CO2-Lip-FA) through the co-encapsulation of PTT/PDT reagents with gas precursor into the hydrophobic and hydrophilic regions of liposomes, respectively, in order to overcome the aggregation issues and substantially improve the synergistic PTT/PDT efficacy. Upon arrival at the tumor region, the PS phototoxicity of Cy/Ce6/CO2-Lip-FA could be effectively switched on through CO2 generation induced by the PTT effect of Cypate upon NIR irradiation. The gas bubble burst can remarkably suppress the aggregation of Cypate/Ce6 and extremely enhance the synergistic PTT/PDT efficacy. These results indicate that the proposed NIR-responsive and gas bubble-functionalized liposomal nanobomb is a highly promising platform for tumor treatment with better therapeutic efficacy.
目前,用于肿瘤治疗的光热疗法(PTT)/光动力疗法(PDT)试剂的原位开关在癌症治疗领域引起了广泛关注。然而,在肿瘤治疗中,实际的PTT/PDT治疗效果在很大程度上受到PTT/PDT试剂从疏水性载体释放到亲水性肿瘤微环境过程中聚集问题的限制。因此,突破由PTT/PDT试剂聚集引起的治疗障碍并实现抗癌效果的实质性提高仍然是一个挑战。在这项工作中,我们通过将PTT/PDT试剂与气体前体分别共包封到脂质体的疏水和亲水区域,开发了一种新型的近红外(NIR)光响应和气泡生成脂质体纳米炸弹(Cy/Ce6/CO2-Lip-FA),以克服聚集问题并大幅提高协同PTT/PDT疗效。到达肿瘤区域后,通过近红外照射下Cypate的PTT效应诱导产生CO2,Cy/Ce6/CO2-Lip-FA的PS光毒性可以有效地开启。气泡破裂可以显著抑制Cypate/Ce6的聚集,并极大地增强协同PTT/PDT疗效。这些结果表明,所提出的近红外响应和气泡功能化脂质体纳米炸弹是一个具有高度前景的肿瘤治疗平台,具有更好的治疗效果。