Preparation of electrospray ALG/PDA-PVP nanocomposites and their application in cancer therapy.

In this study, sodium alginate (ALG)/poly dopamine (PDA)-polyvinylpyrrolidone (PVP) nanocomposites was synthesized via a one-step electrostatic spraying method. The spinning solution of ALG and dopamine was electrostatically sprayed into an alkaline solution of PVP, calcium chloride and tris buffer (pH = 8.5), in which the gelation of ALG and the polymerization of dopamine could be simultaneously triggered. PDA hence produced possesses a high photothermal conversion efficiency, while the PVP that was facilely conjugated onto the surface of nanocomposites improves the colloidal stability and compatibility of the material. Moreover, the ALG renders the nanocomposite excellent drug (doxorubicine, DOX) loading capacity. Promisingly, the temperature increment during the PTT process could promote the DOX release, thus enhancing its therapeutic effect. The in vitro/in vivo biosafety and tumor treatment experiments further corroborate that the ALG/PDA-PVP nanocomposites have remarkable biocompatibility and synergism for tumor hyperthermia and chemotherapy. Consequently, such a one-step electrospray strategy provides a new way for designing nanomaterials and is expected to significantly promote the development of organic photothermal therapeutic agents with excellent bio-compatibility.

Synthesis of cellulose-2,3-bis(3,5-dimethylphenylcarbamate) in an ionic liquid and its chiral separation efficiency as stationary phase.

A chiral selector of cellulose-2,3-bis(3,5-dimethylphenylcarbamate) (CBDMPC) was synthesized by reacting 3,5-dimethylphenyl isocyanate with microcrystalline cellulose dissolved in an ionic liquid of 1-allyl-3-methyl-imidazolium chloride (AMIMCl). The obtained chiral selector was effectively characterized by infrared spectroscopy, elemental analysis and 1H NMR. The selector was reacted with 3-aminopropylsilanized silica gel and the CBDMPC bonded chiral stationary phase (CSP) was obtained. Chromatographic evaluation of the prepared CSPs was conducted by high performance liquid chromatographic (HPLC) and baseline separation of three typical fungicides including hexaconazole, metalaxyl and myclobutanil was achieved using n-hexane/isopropanol as the mobile phase with a flow rate 1.0 mL/min. Experimental results also showed that AMIMCl could be recycled easily and reused in the preparation of CSPs as an effective reaction media.

Integration of Fe3O4 with Bi2S3 for Multi-Modality Tumor Theranostics.

The combination of reactive oxygen species (ROS)-induced chemodynamic therapy (CDT) and photothermal therapy (PTT) holds a promising application prospect for their superb anticancer efficiency. Herein, we created a novel Fe3O4@polydopamine (PDA)@bovine serum albumin (BSA)-Bi2S3 composite as a theranostic agent, by chemically linking the Fe3O4@PDA with BSA-Bi2S3 via the amidation between the carboxyl groups of BSA and the amino groups of PDA. In this formulation, the Fe3O4 NPs could not only work as a mimetic peroxidase to trigger Fenton reactions of the innate H2O2 in the tumor and generate highly cytotoxic hydroxyl radicals (•OH) to induce tumor apoptosis but also serve as the magnetic resonance imaging (MRI) contrast agent to afford the precise cancer diagnosis. Meanwhile, the PDA could prevent the oxidization of Fe3O4, thus supporting the long-term Fenton reactions and the tumor apoptosis in the tumor. The Bi2S3 component exhibits excellent photothermal transducing performance and computed tomography (CT) imaging capacity. In addition, the PDA and Bi2S3 endow the Fe3O4@PDA@BSA-Bi2S3 composite with an excellent photothermal transforming ability which could lead to tumor hyperthermia. All of these merits play the synergism with the tumor microenvironment and qualify the Fe3O4@PDA@BSA-Bi2S3 NPs for a competent agent in the MRI/CT-monitored enhanced PTT/CDT synergistic therapy. Findings in this research will evoke new interests in future cancer therapeutic strategies based on biocompatible nanomaterials.

Synthesis of a Clay-Based Nanoagent for Photonanomedicine.

Photo-induced cancer therapies, mainly including photothermal therapy (PTT) and photodynamic therapy (PDT), have attracted numerous attentions owing to the high selectivity, convenience, and few side effects. However, single PTT usually requires high laser power density, and single PDT usually needs a high photosensitizer dosage. Herein, a kind of composite nanocarrier based on clay (laponite)-polypyrrole (LP) nanodisks was synthesized via the in situ polymerization of pyrrole in the interlayer space of laponite. LP composite nanodisks were then coated with polyvinylpyrrolidone (PVP) to form the LP-PVP (LPP) composite nanodisks which show an excellent colloidal stability and in vitro and in vivo biocompatibility. The interlayer space of LPP can be further used for the loading of Chlorin e6 (Ce6), with an ultrahigh loading capacity of about 89.2%. Furthermore, the LPP nanocarrier can enhance the PDT effect of Ce6 under the irradiation of a 660 nm laser, through enhancing its solubility and cellular uptake amount. Besides, it was found that LPP nanodisks exhibit a more outstanding photothermal performance under a 980 nm near-infrared laser (NIR) than a 808 nm NIR laser, with the photothermal conversion efficiency of 45.7 and 27.7%, respectively. The in vitro and in vivo tumor therapy results evidently confirm that the Ce6-loaded LPP nanodisks have a combined tumor PTT and PDT effect, which can significantly suppress the tumor malignant proliferation.

Preparation of injectable temperature-sensitive chitosan-based hydrogel for combined hyperthermia and chemotherapy of colon cancer.

The purpose of this study was to design an injectable hydrogel with temperature-sensitive property for safe and high efficient in vivo colon cancer hyperthermia and chemotherapy. Chitosan (CS) solution was injected into the tumor at room temperature and automatically gelled after warming to body temperature in the present of ß-glycerophosphate (ß-GP). Combined localized tumor photothermal and chemotherapy were achieved by dissolving photothermal material MoS2/Bi2S3-PEG (MBP) nanosheets and drug molecule doxorubicin (DOX) into the hydrogel, and the gel system could encapsulate DOX and MBP nanosheets and prevent them from entering the blood circulation and damaging normal tissues and cells. More importantly, the CS/MBP/DOX (CMD) hydrogel exhibited a photothermal efficiency of 22.18% and 31.42% in the first and second near infrared light (NIR I and NIR II) biowindows respectively at a low MBP concentration (0.5 mg/mL). Besides, the release of the DOX from CMD hydrogel was controllable since the gel temperature could be governed by NIR laser irradiation. Moreover, the chitosan-based hydrogel had antibacterial effects. The designed composite hydrogel is anticipated to act as a platform for the high efficient treatment of tumors owing to the different penetration depths of NIR I and NIR II.

One-pot synthesis of polypyrrole nanoparticles with tunable photothermal conversion and drug loading capacity.

With an excellent near-infrared (NIR) light-responsive property, polypyrrole (PPy) nanoparticle has emerged as a promising NIR photothermal transducing agent for tumor photothermal therapy (PTT). Herein, we reported the PVP mediated one-pot synthesis of colloidal stable and biocompatible PPy nanoparticles (PPy-PVP NPs) for combined tumor photothermal-chemotherapy. The influence of molecular weight and PVP concentration on the spectroscopic characteristic, photothermal feature, drug loading performance, and antitumor efficiency of the resultant PPy-PVP NPs was systematically studied. By choosing PVP with a molecular weight of 360 kDa (concentration of 5 mg/mL) as the template and surface modifier during the synthesis, PPy-PVP NPs with optimal spectroscopic characteristic, photothermal feature, drug loading performance, and antitumor efficiency were synthesized. Findings in this study are anticipated to provide an in-depth understanding of the important character of surface engineering in the rational design and biomedical applications of PPy NPs.

Preparation of Poly(lactic-co-glycolic acid)-Based Composite Microfibers for Postoperative Treatment of Tumor in NIR I and NIR II Biowindows.

In this work, a novel kind of electrospun microfiber to deliver a photothermal agent and an anticancer drug to tumor sites is explored. Photothermal therapy agent (MoS2 nanosheets) and doxorubicin (DOX) are incorporated with poly(lactic-co-glycolic acid) (PLGA) microfiber via electrospinning a solution of PLGA, MoS2 , and DOX. The designed microfiber with uniform fibrous morphology and negligible in vitro/in vivo hemo-/histo-toxicity is used as a durable photothermal agent, which shows an excellent photothermal transform ability and acceptable photothermal stability in both the first and second near-infrared light (NIR I and II) biowindows. The synergistic in vivo tumor chemotherapy and photothermal therapy efficiency of the composite microfibers are studied in postoperative treatment of cancer. It is found that the tumor postoperative reoccurrence can be completely prohibited owing to the synergistic tumor therapy efficiency in both the NIR I and NIR II biowindows.

[Preparation of large-pore silica microspheres using templating method and their applications to protein separation with high performance liquid chromatography].

Large-pore silica microspheres were synthesized by utilizing weak cation exchange polymer beads as templates, N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride (TMSPTMA) as a structure-directing agent, tetraethoxysilane (TEOS) as a silica precursor, and triethanolamine as a weak base catalyst. The hydrolysis and condensation of the silica precursors occurred inside the templating polymer beads yielded polymer/silica composite microspheres. After the organic polymer templates were removed in the calcination step, large-pore silica microspheres were produced. The effects of different reaction conditions on the morphology, structure and dispersibility of the formed silica microspheres were investigated. It has been shown that when the volume ratio of TMSPTMA, TEOS and triethanolamine was 1:2:2, silica microspheres with pore size range of 50-150 nm and particle size around 2 µm were obtained. The as-prepared silica microspheres were then bonded with chlorodimethyloctadecylsilane (C18), packed into a 50 mm×4.6 mm column, and evaluated for the separations of some common standard proteins and soybean isolation proteins. The results showed that the large-pore silica spheres from this work have potentials for protein separation in HPLC.

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. STATEMENT OF SIGNIFICANCE: A 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.

[A preliminary study of maxillary reconstruction using free fibula-flexor hallucis longus myofascial flap].

OBJECTIVE: To analyze the rationale and feasibility of maxillary reconstruction using free fibula-flexor hallucis longus myofascial flap. METHODS: Nine consecutive cases of maxillary reconstruction using free fibula-flexor hallucis longus myofascial flaps from August of 2002 to August of 2003 were reviewed. Data concerning the operation included description of maxillary defect, design of the fibula flaps, recipient vessel and complications. RESULTS: One flap experienced venous thrombosis after operation, and the flap was salvaged after exploration. All the flaps survived completely with the overall success rate of 100%, as well as the 100% survival of all fibula-flexor hallucis longus myofascial flaps. CONCLUSIONS: Maxillary reconstruction using free fibula-flexor hallucis longus myofascial flap without skin paddle is feasible and reliable.