Tian Libing, Pei Rui, Zhang Xiaojun, Li Kun, Zhong Yuting, Luo Yougen, Zhou Shu-Feng, Chen Lichan
College of Chemical Engineering, Huaqiao University, Xiamen, China.
Department of Basic Medical Science, Jiangsu Vocational College of Medicine, Yancheng, China.
Front Bioeng Biotechnol. 2022 Jul 11;10:934151. doi: 10.3389/fbioe.2022.934151. eCollection 2022.
The inability of small molecule drugs to diffuse into tumor interstitium is responsible for the relatively low effectiveness of chemotherapy. Herein, a hydrogen sulfide (HS) gas-involved chemosensitization strategy is proposed for pancreatic cancer treatment by developing a tumor-specific lipase-responsive nanomedicine based on aptamer-conjugated DATS/Dox co-loaded PCL--PEO micelle (DA/D@Ms-A). After receptor-mediated endocytosis and subsequent digestion of PCL blocks by intracellular lipase, the nanomedicine releases Dox and DATS, which then react with intracellular glutathione to produce HS. The cytotoxicity result indicates that HS can enhance Dox chemotherapy efficiency owing to the synergetic therapeutic effect of Dox and HS. Moreover, the nanomedicine is featured with well tumor penetration capability benefitting from the targeting ability of aptamers and high biocompatibility due to the high density of PEO and biodegradable PCL. The nanomedicine capable of synergetic gas-chemotherapy holds great potential for pancreatic cancer treatment.
小分子药物无法扩散到肿瘤间质中是化疗效果相对较低的原因。在此，通过开发一种基于适配体共轭的DATS/阿霉素共负载聚己内酯-聚环氧乙烷胶束（DA/D@Ms-A）的肿瘤特异性脂肪酶响应纳米药物，提出了一种用于胰腺癌治疗的硫化氢（HS）气体参与的化学增敏策略。在受体介导的内吞作用以及细胞内脂肪酶对聚己内酯嵌段的后续消化后，纳米药物释放出阿霉素和DATS，然后它们与细胞内谷胱甘肽反应生成HS。细胞毒性结果表明，由于阿霉素和HS的协同治疗作用，HS可以提高阿霉素的化疗效率。此外，纳米药物具有良好的肿瘤穿透能力，这得益于适配体的靶向能力，并且由于聚环氧乙烷的高密度和可生物降解的聚己内酯而具有高生物相容性。这种能够进行协同气体化疗的纳米药物在胰腺癌治疗中具有巨大潜力。
