Showing papers by "Luodan Yu published in 2019"

Enhanced Tumor-Specific Disulfiram Chemotherapy by In Situ Cu2+ Chelation-Initiated Nontoxicity-to-Toxicity Transition

Abstract: The antitumor activity of disulfiram (DSF), a traditional US Food and Drug Administration-approved drug for the treatment of "alcohol-dependence", is Cu2+-dependent, but the intrinsic anfractuous biodistribution of copper in the human body and copper toxicity induced by exogenous copper supply have severely hindered its in vivo application. Herein, we report an in situ Cu2+ chelation-enhanced DSF-based cancer chemotherapy technique, using a tumor-specific "nontoxicity-to-toxicity" transition strategy based on hollow mesoporous silica nanoparticles as the functional carrier. Cu2+-doped, DSF-loaded hollow mesoporous silica nanoparticles were constructed for the rapid release of Cu2+ ions induced by the mild acidic conditions of the tumor microenvironment. This resulted in the rapid biodegradation of the nanoparticles and accelerated DSF release once the particles were endocytosed into tumor cells. The resulting in situ chelation reaction between the coreleased Cu2+ ions and DSF generated toxic CuET products and concurrently, Fenton-like reactions between the generated Cu+ ions and the high levels of H2O2 resulted in the production of reactive oxygen species (ROS) in the acidic tumor microenvironment. Both in vitro cellular assays and in vivo tumor-xenograft experiments demonstrated the efficient Cu-enhanced and tumor-specific chemotherapeutic efficacy of DSF, with cocontributions from highly toxic CuET complexes and ROS generated within tumors. This work provides a conceptual advancement of nanoparticle-enabled "nontoxicity-to-toxicity" transformation in tumors, to achieving high chemotherapeutic efficacy and biosafety.

Hypoxia-Irrelevant Photonic Thermodynamic Cancer Nanomedicine

Abstract: The hypoxic tumor microenvironment severely lowers the therapeutic efficacy of oxygen-dependent anticancer modalities because tumor hypoxia hinders the generation of toxic reactive oxygen species. Here we report a thermodynamic cancer-therapeutic modality that employs oxygen-irrelevant free radicals generated from thermo-labile initiators for inducing cancer cell death. A free radical nanogenerator was engineered via direct growth of mesoporous silica layer onto the surface of two-dimensional Nb2C MXene nanosheets toward multifunctionality, where the mesopore provided the reservoirs for initiators and the MXene core acted as the photonic-thermal trigger at the near-infrared-II biowindow (NIR-II). Upon illumination by a 1064 nm NIR-II laser, the photothermal-conversion effect of Nb2C MXene induced the fast release and quick decomposition of the encapsulated initiators (AIPH) to produce free radicals, which promoted cancer cell apoptosis in both normoxic and hypoxic microenvironment. Systematic in vitro and...

Silicene: Wet-Chemical Exfoliation Synthesis and Biodegradable Tumor Nanomedicine.

Abstract: Silicon-based biomaterials play an indispensable role in biomedical engineering; however, due to the lack of intrinsic functionalities of silicon, the applications of silicon-based nanomaterials are largely limited to only serving as carriers for drug delivery systems. Meanwhile, the intrinsically poor biodegradation nature for silicon-based biomaterials as typical inorganic materials also impedes their further in vivo biomedical use and clinical translation. Herein, by the rational design and wet chemical exfoliation synthesis of the 2D silicene nanosheets, traditional 0D nanoparticulate nanosystems are transformed into 2D material systems, silicene nanosheets (SNSs), which feature an intriguing physiochemical nature for photo-triggered therapeutics and diagnostic imaging and greatly favorable biological effects of biocompatibility and biodegradation. In combination with DFT-based molecular dynamics (MD) calculations, the underlying mechanism of silicene interactions with bio-milieu and its degradation behavior are probed under specific simulated physiological conditions. This work introduces a new form of silicon-based biomaterials with 2D structure featuring biodegradability, biocompatibility, and multifunctionality for theranostic nanomedicine, which is expected to promise high clinical potentials.

Photonic cancer nanomedicine using the near infrared-II biowindow enabled by biocompatible titanium nitride nanoplatforms

Abstract: Light-activated photoacoustic imaging (PAI) and photothermal therapy (PTT) using the second near-infrared biowindow (NIR-II, 1000-1350 nm) hold great promise for efficient tumor detection and diagnostic imaging-guided photonic nanomedicine. In this work, we report on the construction of titanium nitride (TiN) nanoparticles, with a high photothermal-conversion efficiency and desirable biocompatibility, as an alternative theranostic agent for NIR-II laser-excited photoacoustic (PA) imaging-guided photothermal tumor hyperthermia. Working within the NIR-II biowindow provides a larger maximum permissible exposure (MPE) and desirable penetration depth of the light, which then allows detection of the tumor to the full extent using PA imaging and complete tumor ablation using photothermal ablation, especially in deeper regions. After further surface polyvinyl-pyrrolidone (PVP) modification, the TiN-PVP photothermal nanoagents exhibited a high photothermal conversion efficiency of 22.8% in the NIR-II biowindow, and we further verified their high penetration depth using the NIR-II biowindow and their corresponding therapeutic effect on the viability of tumor cells in vitro. Furthermore, these TiN-PVP nanoparticles were developed as a contrast agent for NIR-II-activated PA imaging both in vitro and in vivo for the first time and realized efficient photothermal ablation of the tumor in vivo within both the NIR-I and NIR-II biowindows. This work not only provides a paradigm for TiN-PVP photothermal nanoagents working in the NIR-II biowindow both in vitro and in vivo, but also proves the feasibility of PAI and PTT cancer theranostics using NIR-II laser excitation.

Self-evolved hydrogen peroxide boosts photothermal-promoted tumor-specific nanocatalytic therapy

Abstract: The emerging nanocatalytic tumor therapy such as chemodynamic therapy (CDT) converts less harmful hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (˙OH) via metal ion-mediated catalytic Fenton chemistry, which has motivated extensive research interest due to the high specificity of the nanocatalytic reactions to the tumor microenvironment (TME) and minimized side effects. However, traditional CDT substantially suffers from the insufficiency of intratumoral H2O2 for inducing a satisfactory therapeutic efficacy. In this work, we report on a photothermally-promoted Fenton reaction triggered by self-supplied H2O2, based on the constructed two-dimensional (2D) multifunctional therapeutic Nb2C–IO–CaO2 nanoreactors with enhanced therapeutic efficacy and therapeutic biosafety. These Nb2C–IO–CaO2 nanoreactors employ calcium peroxide (CaO2) as a potent H2O2 supplier to sustain the iron oxide (IO) nanoparticle-mediated catalytic Fenton reaction, and to liberate highly toxic ˙OH for inducing tumor-cell apoptosis. Meanwhile, the intratumoral ˙OH production was further promoted by the photothermal effect of the Nb2C–IO–CaO2 nanoreactors under near infrared irradiation at the second biowindow. Extensive in vitro and in vivo evaluations have demonstrated significantly enhanced reactive oxygen species (ROS) production and an outstanding photothermal effect based on these Nb2C–IO–CaO2 nanoreactors, which synergistically lead to elevated therapeutic efficacy. Therefore, this work not only exhibits a promising prospect for reforming the TME to achieve enhanced Fenton reactivity for CDT by elaborately designed nanomaterials with multifunctionality, but also provides novel efficient cancer-therapeutic modalities with simultaneous high therapeutic efficacy and low side effects.

Construction of 2D Antimony(III) Selenide Nanosheets for Highly Efficient Photonic Cancer Theranostics

Abstract: Photonic cancer hyperthermia has been considered to be one of the most representative noninvasive cancer treatments with high therapeutic efficiency and biosafety. However, it still remains a crucial challenge to develop efficient photothermal nanoagents with satisfactory photothermal performance and biocompatibility, among which two-dimensional (2D) ultrathin nanosheets have recently been regarded as the promising multifunctional theranostic agents for photothermal tumor ablation. In this work, we report, for the first time, on the construction of a novel kind of photothermal agents based on the intriguing 2D antimony(III) selenide (Sb2Se3) nanosheets for highly efficient photoacoustic imaging-guided photonic cancer hyperthermia by near-infrared (NIR) laser activation. These Sb2Se3 nanosheets were easily fabricated by a novel but efficiently combined liquid nitrogen pretreatment and freezing-thawing approach, which were featured with high photothermal-conversion capability (extinction coefficient: 33.2 L g-1 cm-1; photothermal-conversion efficiency: 30.78%). The further surface engineering of these Sb2Se3 ultrathin nanosheets with poly(vinyl pyrrolidone) (PVP) substantially improved the biocompatibility of the nanosheets and their stability in physiological environments, guaranteeing the feasibility in photonic antitumor applications. Importantly, 2D Sb2Se3-PVP nanosheets have been certificated to efficiently eradicate the tumors by NIR-triggered photonic tumor hyperthermia. Especially, the biosafety in vitro and in vivo of these Sb2Se3 ultrathin nanosheets has been evaluated and demonstrated. This work meaningfully expands the biomedical applications of 2D bionanoplatforms with a planar topology through probing into new members (Sb2Se3 in this work) of 2D biomaterials with unique intrinsic physiochemical property and biological effect.

Ultrasound/Acidity‐Triggered and Nanoparticle‐Enabled Analgesia

Abstract: Local anesthetics have been extensively employed to treat postoperative pain, but they generally suffer from short acting duration and potential neurotoxicity under high local concentrations, which require the controlled and sustained releasing patterns of treatment drugs. In this work, it is reported, for the first time, the construction of hollow mesoporous organosilica nanoparticles (HMONs)-based nanoplatforms for localized delivery and controlled/sustained release of loaded ropivacaine for local anesthetics, which can be repeatedly triggered by either external ultrasound irradiation or acidity triggering to release the payload, causing on-demand and long-lasting analgesia. Based on the in vivo mouse model of incision pain, the controlled and sustained release of ropivacaine achieves more than six hours of continuous analgesia, which is almost three times longer as compared to single free ropivacaine injection. The low neurotoxicity and high biocompatibility of HMONs for nanoparticle-enabled analgesia are also demonstrated both in vitro and in vivo. This designed/constructed HMONs-based nanoplatform provides a potential methodology for clinical pain management via on-demand and long-lasting pain relief.

Low-toxicity and high-efficiency nano-drug carrier material for tumor therapy and preparation method and application thereof

Abstract: The invention relates to a low-toxicity and high-efficiency nano-drug carrier material for tumor therapy and a preparation method and application thereof. The nano-drug carrier material comprises mesoporous silica and copper ions distributed on the mesoporous silica.