45 research outputs found
Multifunctional bismuth ferrite nanocatalysts with optical and magnetic functions for ultrasound-enhanced tumor theranostics
Ultrasound (US)-assisted oncotherapy has aroused extensive attention due to its capacities to conquer significant restrictions covering short tissue penetration depth and high phototoxicity in photoinduced therapy. We herein developed a class of pure-phase perovskite-type bimetallic oxide, namely, bismuth ferrite nanocatalysts (BFO NCs), for multimodality imaging-guided and US-enhanced chemodynamic therapy (CDT) against malignant tumors. As-prepared BFO nanoparticles with poly(ethylene glycol)-grafted phosphorylated serine (pS-PEG) modification exhibit satisfactory physiological stability and biocompatibility. The BFO NCs also present high fluorescence emission within the second near-infrared region when irradiated with an 808 nm laser. Intriguingly, the BFO NCs demonstrate highly efficient US-enhanced generation of hydroxyl free radicals, as the cavitation bubbles produced by US trigger partial grievous turbulence and promote the transfer rate of the Fenton reagents. Thus, the BFO NCs enable effective inhibition of tumor growth assisted by external US, and the treatment efficacy can be monitored by computer tomography, magnetic resonance, and fluorescence imaging. Meanwhile, H2O2 and US, as a double logic gate, activate the BFO NCs to trigger the iron-catalyzed and US-enhanced CDT with high specificity and treatment efficiency. Therefore, the BFO NCs as a theranostic agent with an enhanced chemodynamic therapeutic effect assisted by external US and a multimodality imaging capacity are put forward, which show a promising prospect for noninvasive chemodynamic oncotherapy.National Research Foundation (NRF)Accepted versionThe work was financially supported by the National Natural Science Foundation of China (51972075, 51772059, and 51972076), the Natural Science Foundation of Shandong Province (ZR2019ZD29), the Heilongjiang Province Postdoctoral Foundation (LBH-Z19129), and the Fundamental Research Funds for the Central Universities. The work was also supported by the Singapore National Research Foundation Investigatorship (NRF-NRFI2018-03)
A smart tumor microenvironment responsive nanoplatform based on upconversion nanoparticles for efficient multimodal imaging guided therapy
Near-infrared (NIR) light-induced imaging-guided cancer therapy has been studied extensively in recent years. Herein, we report a novel theranostic nanoplatform by modifying polyoxometalate (POM) nanoclusters onto mesoporous silica-coated upconversion nanoparticles (UCNPs), followed by loading doxorubicin (DOX) in the mesopores and coating a folate-chitosan shell onto the surface. In this nanoplatform, the core-shell structured UCNPs (NaYF4:Yb,Er@NaYF4:Yb,Nd) showed special upconverting luminescence (UCL) when irradiated with high-penetration 808 nm NIR light, and the doped Yb and Nd ions endowed the sample with CT imaging properties, thus achieving a dual-mode imaging function. Moreover, the simultaneously generated heat mediated by the 808 nm NIR light may coordinate with the chemotherapy generated from the released DOX to realize an efficient synergistic therapy, verified by diverse in vitro and in vivo assays. The coated folate-chitosan shell can target the platform to tumor tissues when it was transported in the blood vessels and accumulated in tumor sites via the enhanced permeability and retention effect (EPR). Due to the acidic and reductive microenvironment of the tumor, the DOX released quickly with the dissolved folate-chitosan shell, exhibiting obvious tumor microenvironment (TME) responsive properties. The smart imaging-guided therapeutic nanoplatform should be highly promising in TME responsive therapy
Hollow Structured Y<sub>2</sub>O<sub>3</sub>:Yb/ErâCu<sub><i>x</i></sub>S Nanospheres with Controllable Size for Simultaneous Chemo/Photothermal Therapy and Bioimaging
To integrate photothermal therapy
(PTT) with chemotherapy for improved
antitumor efficiency, we designed a novel multifunctional composite
by attaching Cu<sub><i>x</i></sub>S nanoparticles onto the
surface of Y<sub>2</sub>O<sub>3</sub>:Yb/Er hollow spheres through
a combined coprecipitation and subsequent hydrothermal route. By altering
the initial pH values for the synthesis of precursors, the size and
structure properties of the final composites can controllably be tuned.
The conjugated folic acid (FA) makes the composite recognize the targeted
cancer cells and the attached Cu<sub><i>x</i></sub>S nanoparticles
endow the composite with photothermal function. It is found that the
release of doxorubicin (DOX) from the functional carrier could be
triggered by both pH value and near-infrared (NIR) radiation. In particular,
both PTT and chemotherapy can be simultaneously driven by 980 nm laser
irradiation. The synergistic therapeutic effect based on PTT and chemotherapy
can lead to low in vitro viability of 12.9% and highly strong inhibition
of animal H22 tumor in vivo, which is superior to any individual therapy.
Moreover, the composite exhibits the clear in vivo red up-conversion
luminescence (UCL). This multifunctional nanocarrier can be applicable
as bioimaging agent and effective antitumor agent for the synergistic
interaction between PTT and the enhanced chemotherapy
Multifunctional Theranostics for Dual-Modal Photodynamic Synergistic Therapy via Stepwise Water Splitting
Combined therapy
using multiple approaches has been demonstrated to be a promising
route for cancer therapy. To achieve enhanced antiproliferation efficacy
under hypoxic condition, here we report a novel hybrid system by integrating
dual-model photodynamic therapies (dual-PDT) in one system. First,
we attached coreâshell structured up-conversion nanoparticles
(UCNPs, NaGdF<sub>4</sub>:Yb,Tm@NaGdF<sub>4</sub>) on graphitic-phase
carbon nitride (<i>g-</i>C<sub>3</sub>N<sub>4</sub>) nanosheets
(one photosensitizer). Then, the as-fabricated nanocomposite and carbon
dots (another photosensitizer) were assembled in ZIF-8 metalâorganic
frameworks through an in situ growth process, realizing the dual-photosensitizer
hybrid system employed for PDT via stepwise water splitting. In this
system, the UCNPs can convert deep-penetration and low-energy near-infrared
light to higher-energy ultravioletâvisible emission, which
matches well with the absorption range of the photosensitizers for
reactive oxygen species (ROS) generation without sacrificing its efficacy
under ZIF-8 shell protection. Furthermore, the UV light emitted from
UCNPs allows successive activation of <i>g</i>-C<sub>3</sub>N<sub>4</sub> and carbon dots, and the visible light from carbon
dots upon UV light excitation once again activate <i>g</i>-C<sub>3</sub>N<sub>4</sub> to produce ROS, which keeps the principle
of energy conservation thus achieving maximized use of the light.
This dual-PDT system exhibits excellent antitumor efficiency superior
to any single modality, verified vividly by in vitro and in vivo assay
Lutecium Fluoride Hollow Mesoporous Spheres with Enhanced Up-Conversion Luminescent Bioimaging and Light-Triggered Drug Release by Gold Nanocrystals
Uniform Na<sub>5</sub>Lu<sub>9</sub>F<sub>32</sub> hollow mesoporous spheres (HMSs) have been successfully
prepared by a facile and mild (50 °C for 5 h) coprecipitation
process, and Au nanocrystals (NCs) with particle size of about 10
nm were conjugated to polyÂ(ether imide) (PEI) modified HMSs by electrostatic
interaction. Compared with Na<sub>5</sub>Lu<sub>9</sub>F<sub>32</sub>:Yb/Er HMSs, the up-conversion (UC) luminescence intensity of Na<sub>5</sub>Lu<sub>9</sub>F<sub>32</sub>:Yb/Er@Au HMSs was much higher
under low pump power due to the local field enhancement (LFE) of Au
NCs, and there is a surface plasmon resonance (SPR) effect with nonradiative
transitions which generates a thermal effect. These two effects have
been proved by theoretical discrete-dipole approximation (DDA) simulation.
The good biocompatibility of Na<sub>5</sub>Lu<sub>9</sub>F<sub>32</sub>:Yb/Er@Au HMSs indicates them as a promising candidate in the biological
field. Particularly, under near-infrared (NIR) laser irradiation,
a rapid doxorubicin (DOX) release was achieved due to the thermal
effect of Au NCs. In this case, Na<sub>5</sub>Lu<sub>9</sub>F<sub>32</sub>:Yb/Er@Au HMSs exhibit an apparent NIR light-controlled âon/offâ
drug release pattern. In addition, UC luminescent images uptaken by
cells show brighter green and red emission under NIR laser excitation.
Therefore, this novel multifunctional (mesoporous, enhanced UC luminescent,
and light-triggered drug release) material should be potential as
a suitable targeted cancer therapy carrier and bioimaging
On-demand generation of peroxynitrite from an integrated two-dimensional system for enhanced tumor therapy
Nanosystem-mediated tumor radiosensitization strategy combining the features of X-ray with infinite penetration depth and high atomic number elements shows considerable application potential in clinical cancer therapy. However, it is difficult to achieve satisfactory anticancer efficacy using clinical radiotherapy for the majority of solid tumors due to the restrictions brought about by the tumor hypoxia, insufficient DNA damage, and rapid DNA repair during and after treatment. Inspired by the complementary advantages of nitric oxide (NO) and X-ray-induced photodynamic therapy, we herein report a two-dimensional nanoplatform by the integration of the NO donor-modified LiYF4:Ce scintillator and graphitic carbon nitride nanosheets for on-demand generation of highly cytotoxic peroxynitrite (ONOOâ). By simply adjusting the Ce3+ doping content, the obtained nanoscintillator can realize high radioluminescence, activating photosensitive materials to simultaneously generate NO and superoxide radical for the formation of ONOOâ in the tumor. Obtained ONOOâ effectively amplifies therapeutic efficacy of radiotherapy by directly inducing mitochondrial and DNA damage, overcoming hypoxia-associated radiation resistance. The level of glutamine synthetase (GS) is downregulated by ONOOâ, and the inhibition of GS delays DNA damage repair, further enhancing radiosensitivity. This work establishes a combinatorial strategy of ONOOâ to overcome the major limitations of radiotherapy and provides insightful guidance to clinical radiotherapy.Agency for Science, Technology and Research (A*STAR)Submitted/Accepted versionFinancial support from the National Natural Science Foundation of China (51972075, 51972076, and 51772059), the Natural Science Foundation of Shandong Province (ZR2019ZD29), the Natural Science Foundation of Heilongjiang Province (YQ2019E014), the Postdoctoral Scientific Research Developmental Fund (LBH-Q18034), and the Ph.D. Student Research and Innovation Fund of the Fundamental Research Funds for the Central Universities (3072020GIP1016) are greatly acknowledged. This research is also supported by the Singapore Agency for Science, Technology and Research (A*STAR) AME IRG grant (A20E5c0081)
La(OH)<sub>3</sub>:Ln<sup>3+</sup> and La<sub>2</sub>O<sub>3</sub>:Ln<sup>3+</sup> (Ln = Yb/Er, Yb/Tm, Yb/Ho) Microrods: Synthesis and Up-conversion Luminescence Properties
One-dimensional LaÂ(OH)<sub>3</sub>:Ln<sup>3+</sup> (Ln
= Yb/Er,
Yb/Tm, Yb/Ho) microrods have been successfully synthesized using molten
composite-hydroxide (NaOH/KOH) as a solvent. La<sub>2</sub>O<sub>3</sub>:Ln<sup>3+</sup> nanostructures with retained striplike shape were
achieved by a subsequent annealing process. The phase, structure,
morphology, and fluorescent properties have been well investigated
by various techniques. It is found that the reaction time plays a
key role in confining the growth of the microrods. Both LaÂ(OH)<sub>3</sub>:Ln<sup>3+</sup> and La<sub>2</sub>O<sub>3</sub>:Ln<sup>3+</sup> nanostructures have rodlike shapes with a typical width of 50â400
nm. The up-conversion (UC) photoluminescence (PL) properties of the
samples have been studied in detail. Under 980 nm laser excitation,
both LaÂ(OH)<sub>3</sub>:Ln<sup>3+</sup> and La<sub>2</sub>O<sub>3</sub>:Ln<sup>3+</sup> microrods exhibit the characteristic emissions of
Er<sup>3+</sup>, Tm<sup>3+</sup>, and Ho<sup>3+</sup> and give green,
blue, and blackish green emission colors, respectively. Additionally,
the doping concentration of Yb<sup>3+</sup> has been optimized by
fixing the Er<sup>3+</sup> concentration. It should be noted that
the up-conversion emission of La<sub>2</sub>O<sub>3</sub>:Er<sup>3+</sup> microrods can be significantly improved in comparison with that
of their bulk counterpart under the same excitation conditions
Highly Uniform 뱉NaYF<sub>4</sub>:Yb/Er Hollow Microspheres and Their Application as Drug Carrier
Highly uniform α-NaYF<sub>4</sub>:Yb/Er hollow microspheres have been successfully prepared via a
simple two-step route. First, the coreâshell structured MF@YÂ(OH)ÂCO<sub>3</sub>:Yb/Er precursor was fabricated by a urea-based homogeneous
precipitation method using colloidal melamine formaldehyde (MF) microspheres
as template. Then the YÂ(OH)ÂCO<sub>3</sub>:Yb/Er precursor was transformed
into hollow NaYF<sub>4</sub>:Yb/Er (α and ÎČ mixed phase)
by a subsequent solvothermal method, and MF microspheres were dissolved
in the solvent simultaneously. The mixed phase of NaYF<sub>4</sub>:Yb/Er was transferred into pure α-NaYF<sub>4</sub>:Yb/Er by
calcination. The as-prepared hollow microspheres were well characterized
by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission
electron microscopy (TEM), energy-dispersive X-ray spectrum (EDS),
Fourier transform infrared spectroscopy (FT-IR), thermogravimetric
analysis (TGA), and upconversion (UC) luminescence spectroscopy. It
is found that the template can be removed without additional calcination
or etching process. α-NaYF<sub>4</sub>:Yb/Er hollow microspheres
exhibit bright upconversion (UC) luminescence under 980 nm laser diode
(LD) excitation. Furthermore, the hollow microspheres show sustained
and pH-dependent doxorubicin hydrochloride (DOX) release properties;
in particular, the emission intensity increases with the release amount
of drug, making the release process able to be tracked or monitored
by the change of the emission intensity, which demonstrates the high
potential of this kind of hollow fluorescent material in drug delivery
fields
Imaging-Guided and Light-Triggered Chemo-/Photodynamic/Photothermal Therapy Based on Gd (III) Chelated Mesoporous Silica Hybrid Spheres
Exploring a combined anticancer therapeutic
strategy to overcome
the limitations of a single mode and pursue higher therapeutic efficiency
is highly promising in both fundamental and clinical investigations.
Herein, a theranostic nanoplatform based on mesoporous silica, which
is functionalized by hybrid nanosphere photosensitizer Chlorin e6
(Ce6), photothermal agent carbon dots (CDs), and imaging agent Gd
(III) ions has been rationally designed and fabricated. A thermo/pH-coupling
sensitive polymer (PÂ(NIPAm-<i>co</i>-MAA)) coated on a composite
acted as a key âgatekeeperâ to control drug release
at the appropriate time and location. Upon light irradiation, two-mode
synergistic therapeutic effect of photodynamic and photothermal therapy
can be achieved by photoactive Ce6 and CDs. Meanwhile, the CDs loaded
in the channels of mesoporous silica hybrid spheres can also play
a role in handling the âgatekeeperâ polymer to control
the drug release process. Combined with the thermo/pH-sensitive drug
release-induced controllable chemotherapy, this platform shows synergistic
therapeutic efficacy better than any single/dual therapy, which is
confirmed with evidence from in vivo and in vitro assays. Considering
the chelated Gd<sup>3+</sup> simultaneously introduced magnetic resonance
imaging (MRI) and computed tomography (CT) properties, this multifunctional
platform should have excellent potential in the imaging-guided cancer
therapy field