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
Abstract
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.
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.