Enhanced Tumor Retention Effect by Click Chemistry for Improved Cancer Immunochemotherapy
Enhanced Tumor Retention Effect by Click Chemistry for Improved Cancer Immunochemotherapy
复制标题
点击化学增强肿瘤保留效果，改善癌症免疫化疗
DOI：
10.1021/acsami.8b02954
复制
发表时间：
2018-05-30
影响因子：
9.5
通讯作者：
He, Qin
中科院分区：
文献类型：
--
作者：
Mei, Ling;Liu, Yayuan;He, Qin
由于肿瘤组织中有限的药物浓度和不适当的治疗策略，肿瘤复发和转移是有效治疗恶性肿瘤的关键挑战。纳米粒有效递送的关键挑战是减少网状内皮系统的摄取并增强渗透性和滞留效应。在此，我们证明了Cu（I）催化的点击化学引发叠氮化物/炔改性胶束的聚集，增强胶束在肿瘤组织中的积累。此外，联合阿霉素与佐剂单磷酰脂质A，toll样受体4的激动剂，产生免疫原性细胞死亡，这进一步促进树突状细胞的成熟，抗原呈递和诱导强效应T细胞在体内。联合抗PD-L1治疗后，显著的抗肿瘤和转移抑制作用是减少PD-L1表达和调节性T细胞。此外，来自记忆T的有效长期免疫保护小鼠免于肿瘤复发。
Because of the limited drug concentration in tumor tissues and inappropriate treatment strategies, tumor recurrence and metastasis are critical challenges for effectively treating malignancies. A key challenge for effective delivery of nanoparticles is to reduce uptake by reticuloendothelial system and to enhance the permeability and retention effect. Herein, we demonstrated Cu(I)-catalyzed click chemistry triggered the aggregation of azide/alkyne-modified micelles, enhancing micelles accumulation in tumor tissues. In addition, combined doxorubicin with the adjuvant monophosphoryl lipid A, an agonist of toll-like receptor4, generated immunogenic cell death, which further promoted maturity of dendritic cells, antigen presentation and induced strong effector T cells in vivo. Following combined with anti-PD-L1 therapy, substantial antitumor and metastasis inhibitory effects were the reduced PD-L1 expression and regulatory T cells. In addition, effective long-term immunity from memory T protected mice from tumor recurrence.