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pH-Sensitive Carbon Dots for Enhancing Photomediated Antitumor Immunity.
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2020-05-14 , DOI: 10.1021/acs.molpharmaceut.0c00227
Da Hye Kim 1 , Jeongdeok Seo 1 , Kun Na 1
Affiliation  

Recent cancer immunotherapy has attracted much attention due to high specificity and recurrence prevention of tumor. Nevertheless, its therapeutic effects are still challenging in solid cancer. To establish superior antitumor immunity, chlorin e6 (Ce6)-loaded pH sensitive carbon dots were investigated (Ce6@IDCDs). At tumoral pH 6.5, Ce6 was released four times compared with the release at physiological pH 7.4 due to an imbalance between hydrophilic and hydrophobic forces via protonation of imidazole groups in Ce6@IDCDs. This result led to the superior singlet oxygen generating activity of Ce6@IDCDs without Ce6 quenching. The maturation effects of dendritic cells after co-incubation with supernatant media obtained from Ce6@IDCDs with laser-treated cells at pH 6.5 were much higher than at physiological pH. Furthermore, Ce6@IDCDs following a laser at pH 6.5 significantly promoted calreticulin exposure and high-mobility group box 1 release, as major immunogenic cell death markers. In bilateral CT-26-bearing mice model, the Ce6@IDCDs elicited significant antitumoral effects at laser treated-primary tumor regions via therapeutic reactive oxygen species. Furthermore, Ce6@IDCDs upon laser irradiation induced a large amount of activated CD8+ T cells, natural killer cells, and mature dendritic cells recruitment into tumoral tissue and hampered tumor growth even at untreated sites approximately four-fold compared with those of others. Overall, this pH-sensitive immunoinducer can accomplish primary and distant tumor ablation via photomediated cancer immunotherapy.

中文翻译:

用于增强光介导的抗肿瘤免疫力的pH敏感碳点。

由于高特异性和防止肿瘤复发,最近的癌症免疫治疗引起了广泛的关注。然而,其治疗效果在实体癌中仍然具有挑战性。为了建立优异的抗肿瘤免疫性,研究了加载了二氢卟酚e6(Ce6)的pH敏感碳点(Ce6 @ IDCD)。在肿瘤pH 6.5时,由于通过Ce6 @ IDCD中咪唑基团的质子化使亲水力和疏水力之间不平衡,因此Ce6的释放是生理pH 7.4的四倍。该结果导致在没有Ce6淬灭的情况下,Ce6 @ IDCD具有优异的单线态氧产生活性。在pH 6.5下,将与Ce6IDCDs获得的上清液培养基和激光处理过的细胞共孵育后,树突状细胞的成熟效果大大高于生理pH值。此外,Ce6 @ IDCDs在pH 6.5的激光下可显着促进钙网蛋白的暴露和高迁移率的box 1释放,这是主要的免疫原性细胞死亡标记。在携带双侧CT-26的小鼠模型中,Ce6 @ IDCDs通过治疗性活性氧在激光治疗的原发性肿瘤区域引起了显着的抗肿瘤作用。此外,Ce6 @ IDCD在激光辐照下会诱导大量活化的CD8+ T细胞,天然杀伤细胞和成熟的树突状细胞募集到肿瘤组织中,甚至在未经治疗的部位,也比其他部位的肿瘤高约四倍,阻碍了肿瘤的生长。总体而言,这种对pH敏感的免疫诱导剂可以通过光介导的癌症免疫疗法完成原发性和远处的肿瘤消融。
更新日期:2020-05-14
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