透明质酸
免疫原性
光动力疗法
肿瘤微环境
化学
癌细胞
肿瘤缺氧
细胞内
体内
活性氧
癌症研究
药理学
癌症
医学
生物化学
免疫系统
免疫学
放射治疗
生物
内科学
有机化学
遗传学
生物技术
作者
Hui Zhang,Yujun Bao,Guanghao Li,Siqi Li,Xiong Zhang,Changhong Guo,Xiaodan Wu,Yingxue Jin
出处
期刊:ACS Biomaterials Science & Engineering
[American Chemical Society]
日期:2024-02-19
卷期号:10 (3): 1379-1392
被引量:1
标识
DOI:10.1021/acsbiomaterials.3c01613
摘要
Cancer metastasis and invasion are closely related to tumor cell immunosuppression and intracellular hypoxia. Activation of immunogenicity and intracellular oxygenation are effective strategies for cancer treatment. In this study, multifunctional nanomicelle hyaluronic acid and cinnamaldehyde is self-assembled into nanomicelles (HPCNPs) were constructed for immunotherapy and tumor cell oxygenation. The Schiff base was constructed of HPCNPs with pyropheophorbide a–Cu (PPa–Cu). HPCNPs are concentrated in tumor sites under the guidance of CD44 proteins, and under the stimulation of tumor environment (weakly acidic), the Schiff base is destroyed to release free PPa. HPCNPs with photodynamic therapeutic functions and chemokinetic therapeutic functions produce a large number of reactive oxygen species (1O2 and •OH) under exogenous (laser) and endogenous (H2O2) stimulations, causing cell damage, and then inducing immunogenic cell death (ICD). ICD markers (CRT and ATP) and immunoactivity markers (IL-2 and CD8) were characterized by immunofluorescence. Downregulation of Arg1 protein proved that the tumor microenvironment changed from immunosuppressive type (M2) to antitumor type (M1). The oxidation of glutathione by HPCNP cascades to amplify the concentration of reactive oxygen species. In situ oxygenation by HPCNPs based on a Fenton-like reaction improves the intracellular oxygen level. In vitro and in vivo experiments demonstrated that HPCNPs combined with an immune checkpoint blocker (α-PD-L1) effectively ablated primary tumors, effectively inhibited the growth of distal tumors, and increased the oxygen level in tumor cells.
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