Researchers at the Changchun Institute of Applied Chemistry, part of the Chinese Academy of Sciences, have developed a new ultrasound-responsive nanocarrier system called S-nanocatchers. This technology enables precise and controllable capture of tumor antigens directly within the body, addressing key challenges faced by traditional antigen-capturing methods in cancer immunotherapy.
The team, led by Professor Xuesi Chen with contributions from Professor Zhaohui Tang and Associate Professor Zhilin Liu, published their findings in CCS Chemistry. Their work seeks to improve personalized tumor vaccines by targeting the problem of high variability in tumor antigens among patients and even within different lesions of a single patient. Traditional vaccine approaches often require complex antigen separation processes that do not address this heterogeneity.
"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," the researchers stated.
Current methods for releasing antigens—such as phototherapy and radiotherapy—have drawbacks including limited tissue penetration and potential harm to healthy tissues. Ultrasound offers deeper penetration and greater compatibility with biological systems but has previously struggled with issues like poor antigen stability and inadequate activation of immune cells known as dendritic cells (DCs).
To overcome these limitations, the researchers designed S-nanocatchers using polyglutamic acid as a backbone combined with a thioether-containing group (S-ACG) and a sonosensitive agent called PPA. These components self-assemble into nanoparticles that protect against non-specific binding during circulation in the bloodstream. When exposed to ultrasound therapy, reactive oxygen species produced by PPA trigger both cell death in tumors (releasing antigens) and oxidation of thioether groups on the nanoparticles. This exposes antigen-catching sites capable of capturing small molecules and peptides from tumors.
A control version without thioether did not show effective antigen binding after ultrasound treatment, supporting the mechanism's reliance on sulfur oxidation. The system also promotes maturation and migration of DCs—crucial steps for stimulating an immune response.
Combining S-nanocatchers with an immune adjuvant called IMDQ resulted in significant outcomes during tests on melanoma mouse models: "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," according to study data.
By increasing infiltration of CD8-positive T cells and boosting cytokines such as IFN-γ and TNF-α, this approach alters the local immune environment around tumors while enabling broader anti-tumor immunity when paired with additional treatments.
"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," researchers explained. They emphasized that their solution addresses non-specific protein binding seen with older technologies while providing new options for tackling cancer diversity and metastasis.
