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.
The narrow absorption and emission bands, long fluorescence
lifetime,
and excellent stability of rare earth nanoparticles (referred to as
RE NPs) make them very attractive for multimodal imaging and therapy
of cancer. Their narrow absorption requires the careful selection
of laser wavelength to achieve the best performance, particularly
for RE NPs simultaneously having photothermal and photoluminescent
properties (e.g., Nd-based nanoparticles), which has not been investigated.
Herein, we prepared a series of different-sized NaNdF4 nanoparticles
(referred to as NNF NPs) (i.e., 4.7, 5.9, 12.8, and 15.6 nm) from
ultrasmall nanoclusters and investigated their in vitro and in vivo size-dependent photothermal conversion
and photoluminescence under irradiation by a 793 nm laser and an 808
nm laser, respectively. We find that all nanoparticles exhibited the
better photothermal conversion performance under the irradiation of
the 808 nm laser than under the 793 nm laser, of which 12.8 nm NNF
NPs showed the best performance, and the temperature of their solution
can be quickly increased from 30 °C to around 60 °C within
10 min under the irradiation of the 808 nm laser with a power intensity
of 0.75 W/cm2. When we used the 793 nm laser to excite
these NNF NPs, we found that all nanoparticles exhibited the stronger
photoluminescence in the second near-infrared window (NIR-II) than
under the excitation by the 808 nm laser, of which 15.6 nm NNF NPs
possessed the strongest NIR-II luminescence. We then modified 12.8
nm NNF NPs with phospholipid carboxyl PEG and functionalized with
RGD for actively targeted imaging of cancer. The NaNdF4@PEG@RGD nanoparticles (referred to as NNF-P-R NPs) have good biocompatibility,
stability, and excellent targeting capability. The in vivo result show that 12.8 nm NNF NPs exhibited better photothermal conversion
performance under the irradiation of the 808 nm laser, and stronger
NIR-II fluorescence under irradiation of the 793 nm laser, which are
consistent with the in vitro result. This work demonstrates
the significance of selection of the proper laser wavelength for maximally
taking advantage of RE nanoparticles for the diagnosis and treatment
of cancer.
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