Shige Wang

A Facile One‐Pot Synthesis of a Two‐Dimensional MoS2/Bi2S3 Composite Theranostic Nanosystem for Multi‐Modality Tumor Imaging and Therapy

2D PEG-ylated MoS2/Bi2 S3 composite nanosheets are successfully constructed by introducing bismuth ions to react with the two extra S atoms in a (NH4)2 MoS4 molecule precursor for solvothermal synthesis of MoS2. The MBP nanosheets can serve as a promising platform for computed tomography and photoacoustic-imaging-guided tumor diagnosis, as well as combined tumor photothermal therapy and sensitized radiotherapy.

Hollow mesoporous organosilica nanoparticles: a generic intelligent framework-hybridization approach for biomedicine.

Chemical construction of molecularly organic-inorganic hybrid hollow mesoporous organosilica nanoparticles (HMONs) with silsesquioxane framework is expected to substantially improve their therapeutic performance and enhance the biological effects beneficial for biomedicine. In this work, we report on a simple, controllable, and versatile chemical homology principle to synthesize multiple-hybridized HMONs with varied functional organic groups homogeneously incorporated into the framework (up to quintuple hybridizations). As a paradigm, the hybridization of physiologically active thioether groups with triple distinctive disulfide bonds can endow HMONs with unique intrinsic reducing/acidic- and external high intensity focused ultrasound (HIFU)-responsive drug-releasing performances, improved biological effects (e.g., lowered hemolytic effect and improved histocompatibility), and enhanced ultrasonography behavior. The doxorubicin-loaded HMONs with concurrent thioether and phenylene hybridization exhibit drastically enhanced therapeutic efficiency against cancer growth and metastasis, as demonstrated both in vitro and in vivo.

Biocompatible PEGylated MoS2 nanosheets: controllable bottom-up synthesis and highly efficient photothermal regression of tumor.

Two-dimensional transition metal dichalcogenides, particularly MoS2 nanosheets, have been deemed as a novel category of NIR photothermal transducing agent. Herein, an efficient and versatile one-pot solvothermal synthesis based on bottom-up strategy has been, for the first time, proposed for the controlled synthesis of PEGylated MoS2 nanosheets by using a novel integrated precursor containing both Mo and S elements. This facile but unique PEG-mediated solvothermal procedure endowed MoS2 nanosheets with controlled size, increased crystallinity and excellent colloidal stability. The photothermal performance of nanosheets was optimized via modulating the particulate size and surface PEGylation. PEGylated MoS2 nanosheets with desired photothermal conversion performance and excellent colloidal and photothermal stability were further utilized for highly efficient photothermal therapy of cancer in a tumor-bearing mouse xenograft. Without showing observable inxa0vitro and inxa0vivo hemolysis, coagulation and toxicity, the optimized MoS2-PEG nanosheets showed promising inxa0vitro and inxa0vivo anti-cancer efficacy.

Injectable 2D MoS2‐Integrated Drug Delivering Implant for Highly Efficient NIR‐Triggered Synergistic Tumor Hyperthermia

MoS2 nanosheets and a doxorubicin (DOX)-containing poly (lactic-co-glycolic acid) (PLGA)/MoS2 /DOX composite implant are successfully constructed based on the unique phase-changing behavior of PLGA/MoS2 /DOX oleosol within tumors. The fast phase transformation can firmly restrict MoS2 and DOX within tumors, and the integrated MoS2 and DOX can endow the implant with high synergistic photothermal and chemotherapeutic efficiency against tumors.

Bi2S3-embedded mesoporous silica nanoparticles for efficient drug delivery and interstitial radiotherapy sensitization

A novel design of Bi2S3 nanoparticles with a coating of mesoporous silica (BMSN) is obtained by a surfactant induced condensation method. It was found that BMSNs exhibited a high doxorubicin (DOX) loading efficiency of 45 wt% and pH-responsive controlled drug release owing to the electrostatic interaction between silanol surface and DOX molecules. The cell viability results demonstrated the encapsulation of DOX into BMSNs could lead to significantly enhanced therapeutic effect against multidrug-resistance cancer cells compared to that of free DOX drug. Furthermore, the comparable study of tumor growth by different treatments demonstrated that the introduction of BMSNs in the X-ray therapy could lead to higher therapeutic effect, with just 2.10-fold increase in tumor volume through 24 days, in comparison to 4.40-fold increase for X-ray beams treatment alone. Meanwhile, the in vitro interstitial radiotherapy experiments demonstrated that the cell inhibiting effect of P-32 interstitial radiotherapy combined with BMSNs (50 μg/mL) was 1.55-fold higher than that of P-32 alone. Significantly, it is notable that the simultaneous chemo- and interstitial radiotherapy based on BMSNs could tremendously increase the therapeutic effect compared to those treatment alone. More importantly, the in vivo P-32 radiotherapy in conjunction with BMSNs was proved to present a significantly eradication of the tumor volumes by an average of 21% reduction to its initial values, in comparison to 2.01-fold increase in case of P-32 treatment alone. Thus, it is expected that the BMSNs could be applied as a highly efficient multifunctional nanosystem to realize the enhanced chemo- and radiotherapy in the further clinical applications.

Perfluoropentane-Encapsulated Hollow Mesoporous Prussian Blue Nanocubes for Activated Ultrasound Imaging and Photothermal Therapy of Cancer

Hollow mesoporous nanomaterials have gained tremendous attention in the fields of nanomedicine and nanobiotechnology. Herein, n-perfluoropentane (PFP)-encapsulated hollow mesoporous Prussian blue (HPB) nanocubes (HPB-PFP) with excellent colloidal stability have been synthesized for concurrent in vivo tumor diagnosis and regression. The HPB shell shows excellent photothermal conversion efficiency that can absorb near-infrared (NIR) laser light and convert it into heat. The generated heat can not only cause tumor ablation by raising the temperature of tumor tissue but also promote the continuous gasification and bubbling of encapsulated liquid PFP with low boiling point. These formed PFP bubbles can cause tissue impedance mismatch, thus apparently enhancing the signal of B-mode ultrasound imaging in vitro and generating an apparent echogenicity signal for tumor tissues of nude mice in vivo. Without showing observable in vitro and in vivo cytotoxicity, the designed biocompatible HPB-PFP nanotheranostics with high colloidal stability and photothermal efficiency are anticipated to find various biomedical applications in activated ultrasound imaging-guided tumor detection and therapy.

Phase-changeable and bubble-releasing implants for highly efficient HIFU-responsive tumor surgery and chemotherapy

CO2 microbubbles (MBs) were explored as smart agent in suppressing tumors. CO2 MBs can be massively produced from the decomposition of an effervescent disintegrant in water. However, the explosive decomposing of the effervescent disintegrant in water will extremely limit its therapeutic applications. The short retention duration of CO2 MBs in blood and the tiny quality of MBs that can leak into tumor sites also severely decrease the tumor therapy efficiency. In this research, a multifunctional poly(lactic-co-glycolic acid) (PLGA)-based solid implant was facilely in situ constructed within tumors based on the liquid-solid phase transition of hydrophobic PLGA/effervescent disintegrant/doxorubicin (DOX) (denoted as PED) oleosol, to effectively control the decomposition of the effervescent disintegrant and increase the accumulation of MBs in the tumor site. The formed PED implant could simultaneously function as a high intensity focused ultrasound (HIFU) enhancement agent and a drug delivery platform featured with HIFU-responsive DOX and spontaneous MBs releasing characteristics. Without HIFU treatment, the hydrophobic PLGA will prevent the contacting of effervescent disintegrant or DOX with water. Under HIFU treatment, water could easily diffuse into the PED implant and thus DOX release, effervescent disintegrant decomposition and CO2 release will be switched on. These CO2 MBs can oscillate with the external focused ultrasound and enhance the mechanical and cavitation effect of focused ultrasound, resulting in an enhanced tumor HIFU ablation towards a VX2 tumor-bearing New Zealand White rabbit. Importantly, it is difficult for effervescent disintegrant and DOX to enter the bloodstream in quantity, therefore, the utilization of CO2 MBs and DOX can be increased and the in vivo biosafety of the implant can be guaranteed. The developed PED implant features easy fabrication, low cost, and excellent in vivo hemo-/histo-compatibility, and holds promising potential for future clinical translation for localized tumor therapy.

Partially PEGylated dendrimer-entrapped gold nanoparticles: a promising nanoplatform for highly efficient DNA and siRNA delivery

Exploring a plasmid DNA (pDNA)/small interfering RNA (siRNA) delivery vector with excellent biocompatibility and high gene transfection efficiency still remains a great challenge. In this research, generation 5 (G5) dendrimer-entrapped gold nanoparticles (Au DENPs) partially modified with polyethylene glycol monomethyl ether (mPEG) were designed as non-viral pDNA/siRNA delivery vectors. The pDNA that can encode luciferase (Luc) or enhanced green fluorescent protein (EGFP) and the Bcl-2 siRNA that can knockdown the expression of the Bcl-2 protein were successfully packaged by the partially PEGylated Au DENPs and effectively delivered into HeLa cells. The length of the surface conjugated mPEG chains and the composition of the entrapped Au NPs were systematically altered to explore their influences on the structure, cytotoxicity, and pDNA or siRNA delivery efficiency. We show that the modified mPEG and entrapped Au NPs can significantly improve the encoding of Luc and EGFP or silence the Bcl-2 protein expression, and the {(Au0)50-G5.NH2-mPEG2K} DENPs display the best DNA or siRNA delivery efficiency among all the designed partially PEGylated Au DENPs. The Luc transfection efficiency of the {(Au0)50-G5.NH2-mPEG2K} was about 292 times higher than that of the G5.NH2 dendrimers at an N/P ratio of 5u2009:u20091, and the Bcl-2 protein was silenced to 15% using the {(Au0)50-G5.NH2-mPEG2K} as a vector relative to the expression level transfected using the G5.NH2 dendrimers (100%). With enhanced pDNA/siRNA transfection efficiency and less cytotoxicity, the PEGylated Au DENPs may hold great promise to be used in pDNA and siRNA delivery applications.

Dendritic Mesoporous Silica Nanospheres Synthesized by a Novel Dual-Templating Micelle System for the Preparation of Functional Nanomaterials

Highly monodisperse, dendritic, and functionalized mesoporous silica nanospheres (MSNs) with sub-200 nm size were synthesized in a one-pot sol-gel reaction, by a dual-templating micelle system consisting of a partially fluorinated short-chain anionic fluorocarbon surfactant and cetyltrimethylammonium bromide. This kind of anionic fluorocarbon surfactant works simultaneously as a swelling agent to enlarge the pore of the MSNs, an ion-pair agent to the structure-directing silane in the preparation of amine-functionalized MSNs, and a surface tension reducing agent to make the system thermodynamically more stable for producing more uniform MSNs. The particle size and the morphology of the resultant MSNs can be fine-tuned by changing the amount of the fluorocarbon surfactant added and the ratio of the functional group containing organosilane to tetraethoxysilane. Subsequently, the as-prepared MSNs were used as base materials for the preparation of drug delivery nanomaterials through the surface grafting of a pH-sensitive drug-conjugated polymer and fluorescent nanomaterials through the embedding of europium(III) complex or the immobilization of large molecule fluorescein isothiocyanate-bovine serum albumin.

Bottom-up synthesis of WS2 nanosheets with synchronous surface modification for imaging guided tumor regression

Two-dimensional transition metal dichalcogenides (TMDs) have been receiving great attention as NIR photothermal transducing agent in tumor photothermal therapy. Keeping in mind the low efficiency of the conventional top-down exfoliated 2D TMDs and the complexity of their surface modifications, we herein proposed a bottom-up strategy for the one-pot hydrothermal and controlled synthesis of surface polyvinyl pyrrolidone (PVP) modified WS2 nanosheets. The material design was based on the chelating-coordinating effect between the lone pair electrons of oxygen of PVP carbonyl group and the unoccupied orbital (5d orbitals) of tungsten. The WS2 nanosheets with synchronous surface PVP grafting showed an excellent photothermal conversion performance, while the surface anchored PVP guaranteed its colloidal stability. Moreover, the strong X-ray attenuation ability and near-infrared (NIR) absorbance of WS2-PVP360kDa enabled the sensitive in vitro and in vivo computed tomography and photoacoustic imaging. The WS2-PVP360kDa nanosheets were biocompatible and exhibited promising in vitro and in vivo anti-cancer efficacy. Findings in this report may greatly promote the design of colloidal stable and biocompatible 2D TMDs and their future clinical translations.nnnSTATEMENT OF SIGNIFICANCEnA bottom-up strategy for the one-pot and controlled synthesis of surface polyvinyl pyrrolidone (PVP) modified WS2 nanosheets was proposed for the first time. By hydrothermally treating the mixture solution of tetrathiotungstate and PVP, Owing to the chelating-coordinating effect between the lone pair electrons of oxygen of PVP carbonyl group and the unoccupied orbital (5d orbitals) of tungsten, PVP was synchronously graphed on WS2-PVP nanosheets surface. The formed WS2-PVP nanosheets were colloidal stable, biocompatible, and exhibited promising computed tomography, photoacoustic imaging and tumor photothermal therapy efficacy both in vitro and in vivo.