具有自氧化和双模态激活的小球藻- hsa生物杂交光声动力免疫治疗

IF 9.7 1区 化学 Q1 ACOUSTICS
Chaoli Xu , Meng Chen , Yiman Zheng , Ning Wang , Wei Lu , Jinhao Dong , Aihua Zhang , Xinhua Ye , Shouju Wang , Zhaogang Teng
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引用次数: 0

摘要

多模式动态疗法通过协同利用活性氧(ROS)介导的细胞毒性来提高精准肿瘤学,例如光动力和声动力模式。然而,它面临着一些关键的挑战,包括缺氧肿瘤、低ROS产量、深层组织渗透能力差和免疫抑制小生境。为了解决这些挑战,我们将小球藻(Chl)设计成一个生物杂交平台,通过顺序整合5,10,15,20-四酰(4-吡啶基)-21H, 23h -四酰卟啉(TPP)和人血清白蛋白(HSA)(称为Chl@TPP/HSA)进行协同光声动力免疫治疗。该系统将Chl的光合氧化能力与TPP的双光声敏特性相结合,从而克服缺氧并增强细胞毒性作用。由于HSA的表面功能化,与未修饰的Chl相比,肿瘤靶向积累提高了6.4倍。体外和体内研究表明,Chl@TPP/HSA在激光和超声(US)照射下可有效诱导免疫原性细胞死亡(ICD),其特征是高迁移率组盒1 (HMGB1)易位、ATP释放和钙网蛋白(CRT)暴露。这些效应协同激活了树突状细胞(DC)成熟(CD80 + CD86 +增加42.5%),增强了自然杀伤细胞(NK)细胞毒性(CD107a +上调59.5%),促进了细胞毒性CD8 + t细胞浸润(增加32.5%),并使巨噬细胞向M1表型极化(CD206 +细胞减少30.7%)。通过协同光声动力免疫疗法,系统给药Chl@TPP/HSA使4t1乳腺癌模型的肿瘤体积减少了91.7%。这些结果建立了Chl@TPP/HSA作为一个集自氧合、双峰ROS生成和免疫调节于一体的多功能平台,为精准肿瘤学提供了有效的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Biohybrid Chlorella-HSA with Self-Oxygenation and Dual-Modal activation for synergistic Photo-Sonodynamic immunotherapy

Biohybrid Chlorella-HSA with Self-Oxygenation and Dual-Modal activation for synergistic Photo-Sonodynamic immunotherapy
Multimodal dynamic therapies enhance precision oncology by synergistically harnessing reactive oxygen species (ROS)-mediated cytotoxicity, as exemplified in photodynamic and sonodynamic modalities. However, it faces key challenges including hypoxic tumors, low ROS yields, poor deep-tissue penetration, and immunosuppressive niches. To address these challenges, we engineered Chlorella vulgaris (Chl) into a biohybrid platform through sequential integration with 5,10,15,20-tetrakis(4-pyridyl)-21H,23H-porphine tetraiodide (TPP) and human serum albumin (HSA) (termed Chl@TPP/HSA) for synergistic photo-sonodynamic immunotherapy. This system integrates the photosynthetic oxygenation capacity of Chl with the dual photo-sonosensitizing properties of TPP, thereby overcoming hypoxia and amplifying cytotoxic effects. Due to surface functionalization with HSA, tumor-targeted accumulation was improved by 6.4-fold compared with that of unmodified Chl. In vitro and in vivo studies demonstrated that Chl@TPP/HSA under laser and ultrasound (US) irradiation effectively induced immunogenic cell death (ICD), which was marked by high mobility group box 1 (HMGB1) translocation, ATP release, and calreticulin (CRT) exposure. These effects synergistically activated dendritic cell (DC) maturation (42.5 % CD80 + CD86 + increase), enhanced natural killer (NK) cell cytotoxicity (59.5 % upregulation of CD107a + ), promoted cytotoxic CD8 + T-cell infiltration (32.5 % increase), and polarized macrophages toward the M1 phenotype (30.7 % reduction in CD206 + cells). Systemic administration of Chl@TPP/HSA achieved a 91.7 % reduction in tumor volume in the 4 T1 breast cancer model via synergistic photo-sonodynamic immunotherapy. These results establish Chl@TPP/HSA as a multifunctional platform that integrates self-oxygenation, dual-modal ROS generation, and immunomodulation, offering an effective strategy for precision oncology.
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来源期刊
Ultrasonics Sonochemistry
Ultrasonics Sonochemistry 化学-化学综合
CiteScore
15.80
自引率
11.90%
发文量
361
审稿时长
59 days
期刊介绍: Ultrasonics Sonochemistry stands as a premier international journal dedicated to the publication of high-quality research articles primarily focusing on chemical reactions and reactors induced by ultrasonic waves, known as sonochemistry. Beyond chemical reactions, the journal also welcomes contributions related to cavitation-induced events and processing, including sonoluminescence, and the transformation of materials on chemical, physical, and biological levels. Since its inception in 1994, Ultrasonics Sonochemistry has consistently maintained a top ranking in the "Acoustics" category, reflecting its esteemed reputation in the field. The journal publishes exceptional papers covering various areas of ultrasonics and sonochemistry. Its contributions are highly regarded by both academia and industry stakeholders, demonstrating its relevance and impact in advancing research and innovation.
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