6 research outputs found
A Versatile Imaging and Therapeutic Platform Based on Dual-Band Luminescent Lanthanide Nanoparticles toward Tumor Metastasis Inhibition
Upconversion
(UC) luminescent lanthanide nanoparticles (LNPs) are
expected to play an important role in imaging and photodynamic therapy
(PDT) <i>in vitro</i> and <i>in vivo</i>. However,
with the absorption of UC emissions by photosensitizers (PSs) to generate
singlet oxygen (<sup>1</sup>O<sub>2</sub>) for PDT, the imaging signals
from LNPs are significantly weakened. It is important to activate
another imaging route to track the location of the LNPs during PDT
process. In this work, Nd<sup>3+</sup>-sensitized LNPs with dual-band
visible and near-infrared (NIR) emissions under single 808 nm excitation
were reported to address this issue. The UC emissions in green could
trigger covalently linked rose bengal (RB) molecules for efficient
PDT, and NIR emissions deriving from Yb<sup>3+</sup> and magnetic
resonance imaging (MRI) were used for imaging simultaneously. Notably,
the designed therapeutic platform could further effectively avoid
the overheating effect induced by the laser irradiation, due to the
minimized absorption of biological media at around 808 nm. TdT-mediated
dUTP nick end labeling (TUNEL) assay showed serious cell apoptosis
in the tumor after PDT for 2 weeks, leading to an effective tumor
inhibition rate of 67%. Benefit from the PDT, the tumor growth-induced
liver and spleen burdens were largely attenuated, and the liver injury
was also alleviated. More importantly, pulmonary and hepatic tumor
metastases were significantly reduced after PDT. The Nd<sup>3+</sup>-sensitized LNPs provide a multifunctional nanoplatform for NIR light-assisted
PDT with minimized heating effect and an effective inhibition of tumor
growth and metastasis
Dual-Mode Imaging-Guided Synergistic Chemo- and Magnetohyperthermia Therapy in a Versatile Nanoplatform To Eliminate Cancer Stem Cells
Cancer
stem cells (CSCs) have been identified as a new target for therapy
in diverse cancers. Traditional therapies usually kill the bulk of
cancer cells, but are often unable to effectively eliminate CSCs,
which may lead to drug resistance and cancer relapse. Herein, we propose
a novel strategy: fabricating multifunctional magnetic Fe<sub>3</sub>O<sub>4</sub>@PPr@HA hybrid nanoparticles and loading it with the
Notch signaling pathway inhibitor <i>N</i>-[<i>N</i>-(3,5-difluorophenacetyl-l-alanyl)]-<i>S</i>-phenylglycinet-butylester
(DAPT) to eliminate CSCs. Hyaluronic acid ligands greatly enhance
the accumulation of the hybrid nanoparticles in the tumor site and
in the CSCs. Both hyaluronase in the tumor microenvironment and the
magnetic hyperthermia effect of the inner magnetic core can accelerate
the release of DAPT. This controlled release of DAPT in the tumor
site further enhances the ability of the combination of chemo- and
magnetohyperthermia therapy to eliminate cancer stem cells. With the
help of polypyrrole-mediated photoacoustic and Fe<sub>3</sub>O<sub>4</sub>-mediated magnetic resonance imaging, the drug release can
be precisely monitored in vivo. This versatile nanoplatform enables
effective elimination of the cancer stem cells and monitoring of the
drugs
Superstable Magnetic Nanoparticles in Conjugation with Near-Infrared Dye as a Multimodal Theranostic Platform
Near-infrared (NIR) dyes functionalized
magnetic nanoparticles (MNPs) have been widely applied in magnetic
resonance imaging (MRI), NIR fluorescence imaging, drug delivery,
and magnetic hyperthermia. However, the stability of MNPs and NIR
dyes in water is a key problem to be solved for long-term application.
In this study, a kind of superstable iron oxide nanoparticles was
synthesized by a facile way, which can be used as <i>T</i><sub>1</sub> and <i>T</i><sub>2</sub> weighted MRI contrast
agent. IR820 was grafted onto the surface of nanoparticles by 6-amino
hexanoic acid to form IR820-CSQ-Fe conjugates. Attached IR820 showed
increased stability in water at least for three months and an enhanced
ability of singlet oxygen production of almost double that of free
dyes, which will improve its efficiency for photodynamic therapy.
Meanwhile, the multispectral optoacoustic tomography (MSOT) and NIR
imaging ability of IR820-CSQ-Fe will greatly increase the accuracy
of disease detection. All of these features will broaden the application
of this material as a multimodal theranostic platform
Rapid Degradation and High Renal Clearance of Cu<sub>3</sub>BiS<sub>3</sub> Nanodots for Efficient Cancer Diagnosis and Photothermal Therapy <i>in Vivo</i>
A key challenge for the use of inorganic
nanomedicines in clinical
applications is their long-term accumulation in internal organs, which
raises the common concern of the risk of adverse effects and inflammatory
responses. It is thus necessary to rationally design inorganic nanomaterials
with proper accumulation and clearance mechanism <i>in vivo</i>. Herein, we prepared ultrasmall Cu<sub>3</sub>BiS<sub>3</sub> nanodots
(NDs) as a single-phased ternary bimetal sulfide for photothermal
cancer therapy guided by multispectral optoacoustic tomography (MSOT)
and X-ray computed tomography (CT) due to bismuthās excellent
X-ray attenuation coefficient. We then monitored and investigated
their absorption, distribution, metabolism, and excretion. We also
used CT imaging to demonstrate that Cu<sub>3</sub>BiS<sub>3</sub> NDs
can be quickly removed through renal clearance, which may be related
to their small size, rapid chemical transformation, and degradation
in an acidic lysosomal environment as characterized by synchrotron
radiation-based X-ray absorption near-edge structure spectroscopy.
These results reveal that Cu<sub>3</sub>BiS<sub>3</sub> NDs act as
a simple but powerful ātheranosticā nanoplatform for
MSOT/CT imaging-guided tumor ablation with excellent metabolism and
rapid clearance that will improve safety for clinical applications
in the future
Use of Synchrotron Radiation-Analytical Techniques To Reveal Chemical Origin of Silver-Nanoparticle Cytotoxicity
To predict potential medical value or toxicity of nanoparticles (NPs), it is necessary to understand the chemical transformation during intracellular processes of NPs. However, it is a grand challenge to capture a high-resolution image of metallic NPs in a single cell and the chemical information on intracellular NPs. Here, by integrating synchrotron radiation-beam transmission X-ray microscopy (SR-TXM) and SR-X-ray absorption near edge structure (SR-XANES) spectroscopy, we successfully capture the 3D distribution of silver NPs (AgNPs) inside a single human monocyte (THP-1), associated with the chemical transformation of silver. The results reveal that the cytotoxicity of AgNPs is largely due to the chemical transformation of particulate silver from elemental silver (Ag<sup>0</sup>)<sub><i>n</i></sub>, to Ag<sup>+</sup> ions and AgāOā, then AgāSā species. These results provide direct evidence in the long-lasting debate on whether the nanoscale or the ionic form dominates the cytotoxicity of silver nanoparticles. Further, the present approach provides an integrated strategy capable of exploring the chemical origins of cytotoxicity in metallic nanoparticles
Gd-Dots with Strong LigandāWater Interaction for Ultrasensitive Magnetic Resonance Renography
Magnetic
resonance imaging contrast agents with both significantly
enhanced relaxivity and minimal safety risk are of great importance
for sensitive clinical diagnosis, but have rarely been reported. Herein,
we present a simple strategy to improve relaxivity by introducing
surface ligands with strong interaction to water molecules. As a proof
of concept, NaGdF<sub>4</sub> nanoparticles (NPs) capped by polyĀ(acrylic
acid) (PAA) show superior relaxivity to those capped by polyethylenimine
and polyethylene glycol, which is attributed to the strong hydrogen-bond
capacity of PAA to water molecules as revealed by theoretical calculation.
Furthermore, benefiting from PAA and ultrasmall particle size, Gd-dots,
namely PAA-capped GdOF NPs (2.1 Ā± 0.2 nm), are developed as a
high-performance contrast agent, with a remarkable ionic relaxivity
of ā¼75 mM<sup>ā1</sup> s<sup>ā1</sup> in albumin
solution at 0.5 T. These Gd-dots also exhibit efficient renal clearance
with <3% of injected amount left 12 h post-injection. Ultrasensitive
MR renography achieved with Gd-dots strongly suggests their great
potential for practical applications