Professor Zhaohui Tang and Associate Professor Zhilin Liu from the team of Professor Xuesi Chen at the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, developed ultrasound-responsive in-situ antigen nanocatchers (S-nanocatchers), achieving precise spatiotemporal capture of tumor antigens and controllable acquisition of in-situ vaccines. This system solves the key problems of traditional antigen-capturing nanocarriers, such as their tendency to non-specifically bind to serum proteins during systemic circulation and their low antigen capture efficiency, providing a novel strategy for personalized tumor immunotherapy. The article was published as an open access Research Article in CCS Chemistry, the flagship journal of the Chinese Chemical Society.
Background information:
The high heterogeneity of tumor antigens in cancer patients is a key limiting factor for improving the efficacy of tumor vaccines, with significant differences in antigen characteristics among different patients and even different lesions within the same patient. In situ tumor vaccine strategies, by directly utilizing endogenous antigens in the tumor microenvironment, eliminate the need for complex antigen separation processes, effectively overcoming this heterogeneity challenge. Currently used antigen release methods such as phototherapy and radiotherapy have limitations, including shallow tissue penetration and potential damage to normal tissues. Ultrasound technology, with its deep penetration and high biocompatibility, has become an ideal stimulus for in situ vaccine development. However, ultrasound-mediated antigen release alone faces challenges such as poor antigen stability and insufficient dendritic cell (DC) presentation, limiting immune activation. Achieving efficient acquisition and precise capture of in situ antigens has become a breakthrough in improving the efficacy of in situ vaccines.
Highlights of this article:
This study designed ultrasound-responsive antigen catchers, S-nanocatchers, with polyglutamic acid (PLG) as the main chain, bonded with a thioether-containing antigen-catching group (S-ACG) and the sonosensitive agent pyrophyllofoetate a (PPA). After self-assembly, the hydrophobic S-ACG and PPA are encapsulated in the nanoparticle core, avoiding non-specific interactions with serum proteins during systemic circulation. When subjected to ultrasound therapy, the reactive oxygen species (ROS) generated by PPA not only induce immunogenic death (ICD) of tumor cells to release antigens, but also oxidize the thioether to hydrophilic sulfones or sulfoxides, exposing the antigen-catching group on the nanoparticle surface, achieving efficient capture of thiol-containing small molecules, peptides, and tumor antigens.
The control group (C-nanocatchers) had its thioether replaced with a carbon chain, and showed no significant antigen-binding ability regardless of whether it was sonicated, confirming the sulfur oxidation-dependent switching mechanism. This system efficiently activates dendritic cell (DC) maturation and migration. Combined with the TLR7/8 agonist IMDQ, it achieved a 93.4% primary tumor inhibition rate and a 60% complete distant tumor regression rate in a B16F10 melanoma mouse model, with no significant systemic toxicity. By enhancing CD8-positive T cell infiltration and the release of cytokines such as IFN-γ and TNF-α, it reshapes the anti-tumor immune microenvironment, providing a universal and precise personalized immunotherapy platform.
Summary and Outlook:
This study combines ultrasound-guided antigen capture with in situ vaccine synthesis, achieving precise spatiotemporal capture of tumor antigens through a "smart switch" mechanism of thioether oxidation, effectively solving the non-specific binding problem of traditional nanocarriers. Ultrasound-responsive antigen catchers (S-nanocatchers) can not only efficiently induce local tumor immune responses but also activate systemic anti-tumor immunity through combination with immune adjuvants, providing a new solution for overcoming tumor heterogeneity and distant metastasis.
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About the journal: CCS Chemistry is the Chinese Chemical Society's flagship publication, established to serve as the preeminent international chemistry journal published in China. It is an English language journal that covers all areas of chemistry and the chemical sciences, including groundbreaking concepts, mechanisms, methods, materials, reactions, and applications. All articles are diamond open access, with no fees for authors or readers. More information can be found at https://www.chinesechemsoc.org/journal/ccschem .
About the Chinese Chemical Society: The Chinese Chemical Society (CCS) is an academic organization formed by Chinese chemists of their own accord with the purpose of uniting Chinese chemists at home and abroad to promote the development of chemistry in China. The CCS was founded during a meeting of preeminent chemists in Nanjing on August 4, 1932. It currently has more than 120,000 individual members and 184 organizational members. There are 7 Divisions covering the major areas of chemistry: physical, inorganic, organic, polymer, analytical, applied and chemical education, as well as 31 Commissions, including catalysis, computational chemistry, photochemistry, electrochemistry, organic solid chemistry, environmental chemistry, and many other sub-fields of the chemical sciences. The CCS also has 10 committees, including the Woman's Chemists Committee and Young Chemists Committee. More information can be found at https://www.chinesechemsoc.org/ .
