Mesoporous carbon nanoparticles embedded with iron in hydrogen-photothermal synergistic therapy.

We developed a new method to synthesize polyethylene glycol modified ultra small iron embedded in mesoporous carbon nanoparticle (C/Fe-PEG NP) for hydrogen (H2) assisted photothermal synergistic therapy. Herein, we use a simple in-situ reduction method to obtain the C/Fe NP in one-step carbonizing process, which is further modified by the biocompatible polyethylene glycol (PEG) on the surface of C/Fe NP to acquire high stability in physiological solutions. Utilizing the excellent photothermal property from the mesoporous carbon and the controllable H2 release property in the weakly acidic tumor microenvironment by the ultra-small Fe, the obtained C/Fe-PEG NPs can effective kill the cancer cells, meanwhile, protect normal cells without drugs. This selective anti-cancer mechanism of C/Fe-PEG NPs may because the produced H2 selective change the mitochondrial energy metabolism. In vivo results prove that the C/Fe-PEG NPs achieve excellent tumor ablation therapeutic effect and normal tissue protecting ability benefit from the H2-assisted photothermal therapy, promising the use of novel nanomaterials with more safety method for future cancer therapy.

Designed formation of Prussian Blue/CuS Janus nanostructure with enhanced NIR-I and NIR-II dual window response for tumor thermotherapy.

Designing photothermal transducing agents (PTAs) with enhanced photothermal conversion efficiency (PCE) holds essential importance for photothermal tumor eradication applications. Currently, it is an effective way to improve the photothermal efficiency by designing the energy level transition leading to the enhancement of UV absorption. To address the challenge, we develop novel Prussian blue@polyacrylic acid/copper sulfide Janus nanoparticles (PB@PAA/CuS JNPs) via selective coating of PAA nano-hemisphere on one of the surfaces of PB NPs followed by the further formation of CuS on the PAA template. The experiments show that the energy level transition occurs between Janus structure. Besides, it offers enhanced absorption over NIR-I and NIR-II dual windows. The muscle tissue penetration studies suggest that the PB@PAA/CuS JNPs have deeper tissue penetration in the 1064 nm laser irradiation group, indicating their potential for treating deep-tissue-seated tumors. In a word, the unique PB@PAA/CuS JNPs show an enhanced tumor inhibitory effect over the NIR-I and NIR-II dual windows, which will open up new opportunities for improving PTT efficiency by the rational nanostructural design of PTAs.

Precise engineering of acorn-like Janus nanoparticles for cancer theranostics.

The anisotropic Janus nanoparticles (JNPs) provide synergistic effects by concentrating multiple properties on a single carrier. Herein, we reported a novel and simple approach to fabricate acorn-like poly(acrylic acid)-mesoporous calcium phosphate/polydopamine (PAA-mCaP/PDA) JNPs, which were selectively functionalized with methoxy-poly(ethylene glycol)thiol (PEG-SH) on PDA domains to obtain superior stability, while the other mCaP sides served as a storage space and passage for the anti-cancer drug of doxorubicin (DOX). The unique acorn-like PAA-mCaP/PDA-PEG JNPs were utilized as novel theranostic agents for photoacoustic (PA) imaging-guided synergistic cancer chemo-phototherapy. More importantly, this synthetic strategy can be applied to synthesize various mesoporous Janus nanocarriers, paving the way toward designed synthesis of acorn-like JNPs in nanomedicine, biosensing and catalysis. STATEMENT OF SIGNIFICANCE: The distinct acorn-like poly(acrylic acid)-mesoporous calcium phosphate/polydopamine Janus nanoparticles (PAA-mCaP/PDA JNPs) with a spherical-shaped PAA-mCaP core and PDA half-shell were fabricated for the first time. To achieve superior stability, the acorn-like PAA-mCaP/PDA JNPs were selectively functionalized with methoxy-poly(ethylene glycol)thiol (PEG-SH) on PDA domains to obtain acorn-like PAA-mCaP/PDA-PEG JNPs. The resultant acorn-like PAA-mCaP/PDA-PEG JNPs own an excellent biocompatibility, high drug-loading contents, good photothermal conversion efficiency, photoacoustic (PA) imaging capacity and pH/NIR dual-responsive properties, enabling the acorn-like JNPs to be applied for PA imaging-guided synergistic cancer chemo-phototherapy. More importantly, the synthetic approach could be extended to prepare acorn-like mesoporous inorganic substances/PDA JNPs for specific applications.

Amphiphilic Janus nanoparticles for imaging-guided synergistic chemo-photothermal hepatocellular carcinoma therapy in the second near-infrared window.

Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors worldwide. With unsatisfactory effects of traditional systematic chemotherapy for HCC owing to its drug resistance, novel therapeutic strategies based on nanomaterials for HCC treatments are promising solutions. To solve the challenges of nanoparticles (NPs)-based drug delivery systems for potential clinical applications, we designed water soluble amphiphilic oleic acid-NaYF4:Yb,Er/polydopamine Au nanoflower Janus NPs (OA-UCNPs/PDA-AuF JNPs) with discrete multi compartment nanostructures as dual-drug delivery systems (DDDSs). This unique nanostructure meets the requirements for containing hydrophobic hydroxycamptothecin/hydrophilic doxorubicin in divided spaces and releasing each drug from non-interfering channels under pH/near-infrared (NIR) dual-stimuli. The amphiphilic DDDSs were utilized to eradicate the tumor burden on a high-fidelity HCC model of a patient-derived xenograft (PDX), and represented an efficient strategy for defeating HCC using multi-modal imaging-guided dual-drug chemo-photothermal therapy in the second NIR window. In addition, the potential mechanisms of action for the DDDSs were evaluated.

Selective Growth Synthesis of Ternary Janus Nanoparticles for Imaging-Guided Synergistic Chemo- and Photothermal Therapy in the Second NIR Window.

Multifunctional therapeutic agents in the second near-infrared (NIR-II) window have attracted wide attention on account of their synergetic properties for effective cancer therapy. Here, we construct a selective growth strategy for the first time to fabricate ternary Janus nanoparticles (JNPs) containing hemispherical MnO2 at one side and Au core covered with CuS shell at opposite side. The obtained ternary JNPs are further modified with poly(ethylene glycol)thiol to enhance the stability and biocompatibility (designated as PEG-CuS-Au-MnO2 ternary JNPs). The MnO2 domain with mesoporous structures can serve as hydrophobic drug carriers and magnetic resonance (MR) imaging contrast agents. Meanwhile, the Au segment is used for X-ray computed tomography (CT) imaging. Moreover, the PEG-CuS-Au-MnO2 ternary JNPs can conduct hyperthermia at 1064 nm in NIR-II window to ablate tumors in deep tissue, which is ascribed to the localized surface plasmon resonance coupling effect of the Au core and CuS domain. All of the results reveal that PEG-CuS-Au-MnO2 ternary JNPs not only exhibit pre-eminent CT/MR imaging capabilities, but also provide high chemo-photothermal antitumor efficacy under the guidance of CT/MR imaging. Taking together, the PEG-CuS-Au-MnO2 ternary JNPs can be regarded as a prospective therapeutic nanoplatform for dual-modal imaging-guided synergistic chemo-photothermal cancer therapy in the NIR-II window.

Rational Design of Branched Au-Fe3 O4 Janus Nanoparticles for Simultaneous Trimodal Imaging and Photothermal Therapy of Cancer Cells.

We report a facile and simple hydrogen reduction method to fabricate PEGylated branched gold (Au)-iron oxide (Fe3 O4 ) Janus nanoparticles (JNPs). Note that the hydrogen induces the formation of Fe3 O4 during the synthesis process. Due to the strong absorption in the near-infrared range, branched Au-Fe3 O4 JNPs showed a significant photothermal effect with a 40 % calculated photothermal transduction efficiency under a laser irradiation of 808 nm in vitro. Owing to their excellent optical and magnetic properties, branched Au-Fe3 O4 JNPs were demonstrated to be advantageous agents for triple-modal magnetic resonance imaging (MRI)/photoacoustic imaging (PAI)/computed tomography (CT) in vitro. Therefore, the synthetic approach could be extended to prepare Au-metallic oxide JNPs for specific applications.

Designed Synthesis of Au/Fe3 O4 @C Janus Nanoparticles for Dual-Modal Imaging and Actively Targeted Chemo-Photothermal Synergistic Therapy of Cancer Cells.

Elaborately designed novel multifunctional Janus nanoparticles (JNPs) have attracted considerable attention owing to their anisotropic surface properties and various functionalities that allow them to house several components for the detection and targeting of cancer cells. In this work, we report a novel and facile approach to synthesize Au/Fe3 O4 @C JNPs, which were further selectively functionalized with amino-poly(ethylene glycol)thiol (NH2 -PEG-SH) and folic acid (FA) on the exposed Au domains to achieve high contrast for X-ray computed tomography (CT) imaging, excellent stability, good biocompatibility, as well as cancer cell-specific targeting. Meanwhile, the other Fe3 O4 @C sides with mesoporous structure served as a drug delivery vehicle for doxorubicin (DOX), an efficient photothermal therapy (PTT) agent, and a magnetic resonance (MR) imaging contrast agent. Taking these features together, these unique multifunctional JNPs provide an intriguing nanoplatform for dual-modal CT and MR imaging-guided actively targeted chemo-photothermal synergistic cancer therapy.

Precise synthesis of unique polydopamine/mesoporous calcium phosphate hollow Janus nanoparticles for imaging-guided chemo-photothermal synergistic therapy.

Multifunctional polymer-inorganic Janus nanoparticles (JNPs) that simultaneously have therapeutic and imaging functions are highly desired in biomedical applications. Here, we fabricated spherical polydopamine/mesoporous calcium phosphate hollow JNPs (PDA/mCaP H-JNPs) via a novel and facile approach. The obtained PDA/mCaP H-JNPs were further selectively functionalized with indocyanine green (ICG) and methoxy-poly(ethylene glycol)thiol (PEG-SH) on PDA domains to achieve a superior photoacoustic (PA) imaging capability and stability, while the other mCaP sides with hollow cavities served as storage spaces and passages for the anti-cancer drug, doxorubicin (DOX). The resultant PEG-ICG-PDA/mCaP H-JNPs possess excellent biocompatibility, a competent drug loading capability, high photothermal conversion efficiency, strong near-infrared (NIR) absorbance, and pH/NIR dual-responsive properties, enabling the H-JNPs to be applied for PA imaging-guided synergistic cancer chemo-phototherapy in vitro and in vivo. Furthermore, the synthetic approach could be extended to prepare PDA/various mesoporous inorganic H-JNPs with spherical shapes for specific applications.

The prevalence and risk factors of stroke in patients with chronic schizophrenia.

OBJECTIVE: To investigate the stroke risk and risk factors in patients with chronic schizophrenia. PATIENTS AND METHODS: This study was a large-sample, cross-sectional survey. A total of 363 patients with chronic schizophrenia were selected from the Changping Traditional Chinese Medicine Hospital, Beijing, in August 2014. The patients were divided into either stroke group or control group based on the presence of stroke. Clinical evaluation included positive and negative syndrome scale assessment and a detailed questionnaire to collect the general information and disease-related conditions. RESULTS: The prevalence of stroke was 16.5% (60 cases). Stroke and control groups showed a significant difference in age, sex, smoking, combined medication, doses, negative factor score in positive and negative syndrome scale, body mass index, waist circumference, and systolic blood pressure. Multivariate analysis showed that a number of factors are significantly related to stroke, including age, sex, smoking, combined medication, doses, body mass index, and systolic blood pressure. CONCLUSION: The prevalence of stroke is relatively higher in Chinese patients with chronic schizophrenia. Chronic schizophrenia patients are more likely to suffer from stroke; meanwhile, a number of risk factors were identified, including old age, female sex, smoking history, combined medication with a variety of drugs, high doses, obesity, and high blood pressure.

Tailored Synthesis of Octopus-type Janus Nanoparticles for Synergistic Actively-Targeted and Chemo-Photothermal Therapy.

A facile, reproducible, and scalable method was explored to construct uniform Au@poly(acrylic acid) (PAA) Janus nanoparticles (JNPs). The as-prepared JNPs were used as templates to preferentially grow a mesoporous silica (mSiO2 ) shell and Au branches separately modified with methoxy-poly(ethylene glycol)-thiol (PEG) to improve their stability, and lactobionic acid (LA) for tumor-specific targeting. The obtained octopus-type PEG-Au-PAA/mSiO2 -LA Janus NPs (PEG-OJNP-LA) possess pH and NIR dual-responsive release properties. Moreover, DOX-loaded PEG-OJNP-LA, upon 808 nm NIR light irradiation, exhibit obviously higher toxicity at the cellular and animal levels compared with chemotherapy or photothermal therapy alone, indicating the PEG-OJNP-LA could be utilized as a multifunctional nanoplatform for in vitro and in vivo actively-targeted and chemo-photothermal cancer therapy.

The facile synthesis of hollow Au nanoflowers for synergistic chemo-photothermal cancer therapy.

A novel, mild and facile synthetic route was first developed to fabricate hollow Au nanoflowers (designated as H-AuNFs) with drug loading capacity, superior photothermal conversion property and pH/NIR dual-responsive drug delivery performance.