Table 1.
Nanomaterials targeting senescent cells using cellular in vitro and in vivo models.
Nanomaterial | Biologically- Active Component |
Concentration | Senescence Model | In Vitro/In Vivo Model | Senolytic Effects and Mechanism | Ref. |
---|---|---|---|---|---|---|
LR-CD9mAb CD9 monoclonal antibody conjugated to PEGylated liposomes | Rapa | 25 nM | Human dermal fibroblasts (HDF), doxorubicin-induced senescence | In vitro | Anti-senescence activity (increased proliferative potential, decreased β-galactosidase activity and p53/p21 expression, and increased cell migration) | [118] |
CD9-Lac/CaCO3/Rapa NPs CD9 monoclonal antibody-conjugated lactose-wrapped calcium carbonate nanoparticles loaded with rapamycin | Rapa | 0.2 mg of rapamycin per mg of CaCO3 NPs | Human dermal fibroblasts (HDF), replicative and doxorubicin-induced senescence | In vitro | Anti-senescence activity (decreased β-galactosidase activity and p53/p21/CD9/cyclin D1 expression, increased cell proliferation and cell migration ability, decreased population doubling time, and prevention of G1 cell cycle arrest) | [107] |
MoS2 NPs molybdenum disulfide mesoporous silica nanoparticles | - | 50 μg/mL | Human aortic endothelial cells (HAECs), stress-induced premature senescence | In vitro | Anti-senescence activity (decreased γ−H2AX phosphorylation, repressed upregulation of p16, p21 and p53, activation of autophagy, improved autophagic flux, and prevention of lysosomal and mitochondrial dysfunction) | [108] |
GalNP(dox) 6-mer galacto-oligosaccharide encapsulated doxorubicin | Dox | 1 mg/kg | Mouse, bleomycin-induced lung fibrosis | In vivo | Anti-senescence activity (improved lung function) | [109] |
GalNP(nav) 6-mer galacto-oligosaccharide encapsulated navitoclax | Nav | 0.06 mg/mL | Melanoma (SK-MEL-103), palbociclib-induced senescence | In vitro | Senolytic activity (apoptosis of senescent cells) | |
GalNP(dox) 6-mer galacto-oligosaccharide encapsulated doxorubicin | Dox | 1 mg/kg | Mouse-bearing SK-MEL-103 tumor xenografts, palbociclib-induced tumor senescence | In vivo | Clearance of senescent cells and induced regression of tumor xenografts | |
GalNP(nav) 6-mer galacto-oligosaccharide encapsulated navitoclax | Nav | |||||
DSAs Docetaxel-tannic acid self-assemblies (DSAs)-based nanoparticles | Docetaxel | 2.5-5 nM | Prostate cancer cells (C4-2 and PC- 3) | In vitro | Senolytic activity (inhibition of senescence-related TGFβR1, FOXO1, and p21 proteins and activation of apoptosis) | [119] |
30 mg/kg | Mouse-bearing PC-3 tumor xenografts | In vivo | Clearance of senescent cells (induced regression of tumor xenografts by blockade of TGFβR1/p21-mediated senescence signaling and activation of apoptosis) | |||
NanoMIPs molecularly-imprinted nanoparticles | Dasatinib | 10 μM dasatinib-conjugated B2M nanoMIPs | Bladder cancer cells with a tetracycline (tet)-regulatable p16 expression systems (EJp16) | In vitro | Senolytic activity (decreased number of senescent cancer cells) | [110] |
MNPQ quercetin surface-functionalized Fe3O4 nanoparticles | Quercetin | 5 μg/mL | Human foreskin fibroblasts (BJ), hydrogen peroxide-induced senescence | In vitro | Senolytic and senostatic activity (AMPK activation, induction of non-apoptotic cell death, and inhibition of SASP components, namely IL-6 and IFN-β) | [120] |
GalNP(nav) | Nav | 40 mg GalNP (Nav)/kg (≈2.5 mg/kg of free navitoclax) | Triple-negative breast cancer mouse model, palbociclib-induced senescence | In vivo | Senolytic activity (inhibited tumor growth, reduced metastasis, and limited systemic toxicity of navitoclax, and apoptosis of senescent cancer cells) | [121] |
Abbreviations: Rapa, rapamycin; Dox, doxorubicin; Nav, navitoclax.