Detecting and targeting senescent cells using molecularly imprinted nanoparticles

Abstract

The progressive accumulation of senescent cells in tissues in response to damage importantly contributes to pathophysiological conditions such as fibrosis, diabetes, cancer, Alzheimer's and ageing. Consistent with this, eliminating senescent cells prolongs the lifespan and healthspan in animals and ameliorates certain diseases. Detecting and clearing senescent cells from human tissues could therefore have a significant diagnostic and prognostic impact. However, identifying senescent cells in vivo has proven to be complex. To address this, we characterized and validated a panel of novel membrane markers of senescence. Here, we show the application of molecularly imprinted nanoparticles (nanoMIPs) against an extracellular epitope of one of these markers, B2M, to detect senescent cells in vitro and in vivo. We show that nanoMIPs do not elicit toxic responses in the cells or in mice and successfully recognize old animals, which have a higher proportion of senescent cells in their organs. Importantly, nanoMIPs loaded with drugs can specifically kill senescent cells. Our results provide a proof-of-principle assessment of specific and safe nanotechnology-based approaches for senescent cell detection and clearance with potential clinical relevance.