An Antibody-directed and Immune Response Modifier-augmented Photothermal Therapy Strategy Relieves Aging via Rapid Immune Clearance of Senescent Cells

Aging Dis. 2024 Apr 1;15(2):787-803. doi: 10.14336/AD.2023.0628-1.

Abstract

Cellular senescence is an irreversible and multifaceted process inducing tissue dysfunction and organismal aging, and thus the clearance of senescent cells can prevent or delay the onset of aging-related pathologies. Herein, we developed an augmented photothermal therapy strategy integrated with an antibody against β2-microglobulin (aB2MG) and an immune adjuvant imiquimod (R837) to effectively accelerate senescent cell apoptosis and clearance under a near-infrared light. With this strategy, the designed CroR@aB2MG enables the targeting of senescent cells and the application of photothermal therapy concomitantly, the initiation of immune clearance subsequently, and finally the realization of protective effects against senescence. Our results showed that the photo-induced heating effect caused senescent cells to quickly undergo apoptosis and the synchronous immune response accelerated the clearance of senescent cells in vitro and in vivo. Therefore, this photoactivated speedy clearing strategy may provide an efficient way for the treatment of senescence-related diseases by eliminating senescent cells with biomaterials.

MeSH terms

  • Antibodies*
  • Cellular Senescence
  • Immunity
  • Photothermal Therapy*

Substances

  • Antibodies

Grants and funding

This work was financially supported by National Key R&D Program of China (2018YFA0109800). CAMS Innovation Fund for Medical Sciences (2022-I2M-1-012, 2021-I2M-1-051), National Natural Science Foundation of China (81971324, 81902848, 82102444), Key-Area Research and Development Program of Guangdong Province (2021B0909060001), 2021 General Research Institute for Nonferrous Metals "Unveiling and Commanding" Project (2021JC0103, 2020YFA0113000, 2020YFA0113001), Supported by the 111 Project (B180 07).