Bioorthogonal/Ultrasound Activated Oncolytic Pyroptosis for Augmented In Situ Tumor Vaccination

Date:26-04-2024   |   【Print】 【close

The development of personalized tumor vaccines has shown great promise in the field of cancer immunotherapy. However, the effectiveness of in situ tumor vaccines, which are derived from immunogenic cancer cell death (ICD), is hindered by inadequate immunogenicity and the presence of an immunosuppressive tumor microenvironment (TME), resulting in suboptimal activation of antitumor immunity. 

Recently, a research team led by Prof. CAI Lintao from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences has developed a series of membrane-localized tetrazine-functionalized Ruthenium (II) sonosensitizers for establishing a bioorthogonal-activated in situ tumor vaccine in an efficient and safe way.  

The study was published in ACS Nano on Mar. 24. 

In this study, the well-designed bioorthogonal-activated sonosensitizers could induce intensive membrane disruption with localized produced type I and II reactive oxygen species (ROS) under ultrasound irradiation.

"This membrane disruption could evoke remarkable oncolytic pyroptosis to potentiate sonodynamic therapy (SDT) performance and maximize tumor immunogenicity," said Prof. CAI. 

To broaden the application of this bioorthogonal-driven pyroptosis induction strategy in various types of tumors, the researchers developed a universal bioorthogonal artificial-targeting strategy based on stimuli-responsive nanoplatforms, which reinforce the feasibility and biosafety of the oncolytic pyroptosis induction strategy. The ultrasound-triggered oncolytic pyroptosis has been demonstrated to enhance systemic antitumor immunity, inhibiting the growth of primary and distant tumors, as well as suppressing tumor metastasis and recurrence. 

This work provides a novel strategy to pursue oncolytic pyroptosis and convert tumor into in situ vaccine factory for boosted antitumor immunity.  

Figure 1. Bioorthogonal/Ultrasound Activated Oncolytic Pyroptosis for Augmented In Situ Tumor Vaccination. (Image by SIAT) 

Figure 2. (A) Schematic Illustration of Fabrication of GSH-Responsive HSA@BCN and Acid-Responsive HSA@Tz-Ru1. (B) Schematic Illustration of Bioorthogonal-Activated Membrane-Targeting SDT Modality to Precisely Evoke Oncolytic Pyroptosis and Convert Localized Tumor into In Situ Vaccine Factory for Boosted Antitumor Immunity. (Image by SIAT) 


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ZHANG Xiaomin