A Binary siRNA-Loaded Tetrahedral DNA Nanobox for Synergetic Anti-Aging Therapy

Extensive accumulation of senescent cells contributes to organismal aging, and slowing down the process of cellular senescence may ameliorate age-related pathologies. Targeted inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) is found to suppress the conversion of cells to senescence. The regulatory-associated protein of mTOR (Raptor), a key component of mTORC1, has been implicated as important in the aging process, and its druggability deserves to be investigated. Due to high efficiency and high convenience in drug construction, siRNA shows great potential in silencing Raptor expression via RNA interfering therapy. Here, we developed a functionalized anti-aging nanoplatform based on tetrahedral DNA nanostructures (TDNs) encapsulating siRNA targeting Raptor for synergistic anti-aging therapy, named siR-TDN_box. Anti-inflammatory and antioxidant properties of TDN beneficially attenuate age-associated inflammation while serving as siRNA nanocarrier, and thus play a binary role. The results suggest that the siR-TDN_box binary therapeutic nanoplatform has demonstrated an excellent ability to delay aging, inhibit mTORC1 signaling, and extend lifespan. This anti-aging nanoplatform may provide a medium for the combined application of traditional senotherapeutic drugs and promote the upgrading of nanomaterials with anti-aging effects.