The photodynamic therapy (PDT) as a promising antitumor therapy technique is greatly hampered by the low tissue penetration of light and the photothermal effect of prolonged irradiation. Near-infrared (NIR) persistent luminescence nanoparticles (NPLNPs) possess the potential for application in next-generation PDT. However, owing to the low re-excitation efficiency of NPLNPs in deep tissue, the current PDT nanoplatform based on NPLNPs is faced with the disadvantage of decreased PDT efficiency induced by persistent luminescence (PersL) decay at the lesion site. Herein, NPLNPs, Zn1.3Ga1.4Sn0.3O4:Cr3+ (ZGS), with small particle sizes and excellent optical properties are synthesized via a simple acetylacetonate combustion method. The ZGS can be repeatedly excited by the biological window (659 nm) light to produce a strong NIR (700 nm) PersL. The response efficiency of ZGS to the wavelength in the biological window has been greatly improved by doping Sn4+ into the ZnGa2O4 matrix, which is 55 times higher than that of traditional ZnGa2O4:Cr3+. We further develop a PDT nanoplatform by modifying a photosensitizer on its surface. The PDT experiments show that the developed nanoplatform can achieve continuous and efficient tumor PDT with a depth of up to 3 cm by repeated excitation using a 659 nm LED. The NPLNPs largely solve the problem of the low re-excitation efficiency after NIR PersL decay of traditional NPLNPs in deep tissue applications and will further promote the application of NIR PLNPs in the biomedical field.
Abstract Background Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. Results In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo . Conclusions In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)