Dye‐Sensitized Rare Earth Nanoparticles with Up/Down Conversion Luminescence for On‐Demand Gas Therapy of Glioblastoma Guided by NIR‐II Fluorescence Imaging

Abstract

As the primary malignant tumor in the brain, glioblastoma exhibits a high mortality due to the challenges for complete treatment by conventional therapeutic methods. It is of great importance to develop innovative therapeutic agents and methods for treatment of glioblastoma. In this work, the imaging and therapy of glioblastoma are reported by using dye sensitized core‐shell NaYF4:Yb/Tm@NaYF4:Nd nanoparticles with strong up/down‐conversion luminescence, of which the ultraviolet up‐conversion emissions at 348 and 365 nm are significantly enhanced by nearly 28 times and used to control the release of SO2 from 5‐Amino‐1,3‐dihydrobenzo[c]thiophene 2,2‐dioxide prodrug for gas therapy, and the second near‐infrared (NIR‐II) down conversion emission at 1340 nm is increased five times and applied for imaging. It is revealed that the released SO2 molecules not only cause oxidative stress damage of tumor cells, but also induce their pro‐death autophagy by down‐regulating the expression of p62 and up‐regulating the ratio of LC3‐II/LC3‐I, ultimately inhibiting tumor growth. The work demonstrates the great potential of rare earth nano‐platform with functions of NIR‐II imaging and photo‐controlled gas therapy in the diagnosis and treatment of orthotopic glioblastoma.

Reducing Chemo-/Radioresistance to Boost the Therapeutic Efficacy against Temozolomide-Resistant Glioblastoma

“…To generate SO 2 on demand under UV irradiation, we selected 5-amino-1,3-dihydrobenzo­[ c ]­thiophene 2,2-dioxide (ATD) as a precursor. , As shown in Figure d, the radioluminescence of the core–shell NaYF 4 :Ce@NaLuF 4 :Nd nanoparticles overlapped well with the UV–vis absorption of ATD, indicating the possibility of controlling the release of SO 2 from ATD by the UV light converted from X-ray through our nanoscale scintillators. To prove this concept, we modified and functionalized NaYF 4 :Ce@NaLuF 4 :Nd nanoparticles with ATD by the ligand-exchange and coordination strategies.…”

“…The fabrication of core–shell NaYF 4 :Ce@NaLuF 4 :Nd nanoscale scintillators (ScNPs) and their application in the X-ray-triggered generation of SO 2 to boost the therapy of GBM by reducing the chemo-/radioresistance are illustrated in Scheme . Both the NaYF 4 :Ce cores and core–shell NaYF 4 :Ce@NaLuF 4 :Nd nanoparticles were prepared using a protocol described elsewhere. , The obtained NaYF 4 :Ce cores and NaYF 4 :Ce@NaLuF 4 :Nd core–shell nanoparticles were monodispersed, and their average sizes were 18.3 and 22.8 nm, respectively (Figures a,b and S1a,b). High-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) images of core–shell NaYF 4 :Ce@NaLuF 4 :Nd nanoparticles showed that the lattice fringe spacing of the hexagonal NaYF 4 core (100) was 0.5 nm, and the thickness of the shell was 2.25 nm (Figure S1c).…”

“…5-Amino-1,3-dihydrobenzo [c] thiophene 2,2-dioxide (ATD) was purchased from Beijing J&k Technology Co. Ltd. All reagents for qRT-PCR were purchased from Hangzhou Bioer Technology Co. Ltd. and Vazyme Biotech Co. Ltd. Additional reagent information is provided in our previous studies. , …”

Management of fluorescent organic/inorganic nanohybrids for biomedical applications in the NIR-II region

“…11A). 62,64,98,99 Due to their abundant 4f energy level configuration, RENPs with narrow (B10 nm) and small absorption cross section (B10 À20 cm À2 ), and nonblinking narrow band emission are widely used as inorganic species in this strategy. 19 Organic species are generally cyanine dyes with a large absorption cross section (10 À16 cm À2 for ICG), which act as light harvesting antenna.…”

Temozolomide Efficacy and Metabolism: The Implicit Relevance of Nanoscale Delivery Systems

“…These results indicate the possibility of slowing down glioblastoma development by means of drug therapy. However, the severity of the condition and the efficacy characteristics of existing drugs indicate the need to search for fundamentally new methods of drug therapy for glioblastoma [ 32 , 33 , 34 ].…”