Inflammation and Acinar Cell Dual-Targeting Nanomedicines for Synergistic Treatment of Acute Pancreatitis via Ca2+ Homeostasis Regulation and Pancreas Autodigestion Inhibition.

Severe acute pancreatitis (AP) is a life-threatening pancreatic inflammatory disease with a high mortality rate (∼40%). Existing pharmaceutical therapies in development or in clinical trials showed insufficient treatment efficacy due to their single molecular therapeutic target, poor water solubility, short half-life, limited pancreas-targeting specificity, etc. Herein, acid-responsive hollow mesoporous Prussian blue nanoparticles wrapped with neutrophil membranes and surface modified with the N,N-dimethyl-1,3-propanediamine moiety were developed for codelivering membrane-permeable calcium chelator BAPTA-AM (BA) and trypsin activity inhibitor gabexate mesylate (Ga). In the AP mouse model, the formulation exhibited efficient recruitment at the inflammatory endothelium, trans-endothelial migration, and precise acinar cell targeting, resulting in rapid pancreatic localization and higher accumulation. A single low dose of the formulation (BA: 200 µg kg-1, Ga: 0.75 mg kg-1) significantly reduced pancreas function indicators to close to normal levels at 24 h, effectively restored the cell redox status, reduced apoptotic cell proportion, and blocked the systemic inflammatory amplified cascade, resulting in a dramatic increase in the survival rate from 58.3 to even 100%. Mechanistically, the formulation inhibited endoplasmic reticulum stress (IRE1/XBP1 and ATF4/CHOP axis) and restored impaired autophagy (Beclin-1/p62/LC3 axis), thereby preserving dying acinar cells and restoring the cellular "health status". This formulation provides an upstream therapeutic strategy with clinical translation prospects for AP management through synergistic ion homeostasis regulation and pancreatic autodigestion inhibition.

Transcutaneous amorphous preparation co-delivering curcumin and modified aptamer as a synergistic approach for the amelioration of psoriasis-like skin inflammation.

The aim is to achieve the targeting function of Aptamer 21-2 (Apt) by modifying glycyrrhizic acid (GA) to obtain Apt-GA and by delivering it through mesoporous silica in µm-size (µmS). Moreover, it is planned to induce synergistic effects of the novel amorphous preparation of Apt-GA with curcumin (Cur) in the treatment of psoriasis. UV/vis spectrophotometric analysis and Fourier transform infrared spectroscopy were performed to demonstrate the linkage of Apt and GA. The replacement of GA with Apt-GA in GA-Cur-µmS did not make a difference in the amorphous state, but showed superior fluorescence of Cur in the inflamed dermis similar to psoriatic induced by imiquimod. Consequently, compared to GA-Cur-µmS and Apt, Apt-GA-Cur-µmS exhibited less pronounced psoriatic characteristics in vivo, including Psoriasis Area and Severity Index, histological image, immunohistochemistry and immuno-fluorescence labeling neutrophils. The enzyme-linked immunosorbent assay showed a similar phenomenon that less IL-17A was observed after treatment with Apt-GA-Cur-µmS than with GA-Cur-µmS or Apt. Our finding suggests that this novel Apt delivery system achieved the Apt targeting function in the dermis by taking advantage of GA and µmS, and exhibited synergistic anti-psoriatic effect by co-delivering curcumin.

Heparin modified graphene oxide for pH-sensitive sustained release of doxorubicin hydrochloride.

A novel nanocarrier of heparin (Hep) modified graphene oxide (GO) was fabricated via a linker (adipic dihydrazide) and used as a pH-sensitive drug delivery system for controlling the release of anticancer drug doxorubicin (DOX) for anti-tumor therapy. The finally obtained nanocarrier was GO-ADH-Hep with better stability, blood compatibility and biocompatibility confirmed by the hemolytic test and in vitro cytotoxicity study. Its safety issue was greatly improved via Hep modification. The amount of DOX loaded onto GO-ADH-Hep was significantly high and dependent on pH value. The release rate of DOX from GO-ADH-Hep/DOX was pH-sensitive and much-slower than that of free DOX solution suggesting the sustained drug-release capacity of this prepared nanocomplexes. In addition, the results of cytotoxicity study illustrated that this fabricated nanocomplexes displayed effective cytotoxicity to MCF-7 and HepG2 cells. What's more, the results of the in vivo pharmacokinetic study was also indicated that the GO-ADH-Hep/DOX nanocomplexes could significantly prolong the retention time of DOX in vivo and this was consistent with the in vitro drug release performance. And finally, according to the biodistribution study, DOX delivered by GO-ADH-Hep could reduce cardiotoxicity deriving from DOX solution and also decrease the pulmonary toxicity deriving from unmodified GO. Based on the in vitro and in vivo investigations, the fabricated GO-ADH-Hep could be a promising candidate as an ideal nano-carrier for drug delivery and anti-cancer therapy.

Recent Developments of Phototherapy Based on Graphene Family Nanomaterials.

Graphene-based nanomaterials have drawn abundant interest in various fields such as biomedicine in recent years. Thanks to the ultra-high surface area of single-layered graphene, higher molecular loading is obtained. In addition, easy modifications were acquired because of its ample oxygen-content functional groups. Owing to its excellent physical- chemical properties, graphene-based nanomaterials have been widely explored as novel nanovectors for disease theranostics. In this article, we gave a comprehensive review of graphenebased nanomaterials, including introduction about different members of graphene family nanomaterials (GFNs), various modifications, toxicity and biomedical applications of graphene- based derivatives. More attentions were given to phototherapy in this paper. The mechanisms of photothermal and photodynamic therapy were also offered. Finally, the prospects and challenges of the graphene-based nanomaterials were discussed in this review.

Tunable dual-wavelength fiber laser with ultra-narrow linewidth based on Rayleigh backscattering.

Dual-wavelength fiber lasers with ultra-narrow linewidth find wide applications in high-speed optical communications, fiber optic sensors, high resolution measurements and medical instruments and microwave or terahertz generation systems. Based on the linewidth compression mechanism due to Rayleigh backscattering, this paper adopts a simple ring structure cooperated with two fiber Bragg gratings centered at 1550 nm and 1530 nm respectively, achieving a dual-wavelength fiber laser with ultra-narrow linewidth, with a 3dB linewidth of ~700 Hz for each wavelength, and the SNR of 60dB. Tuning the center wavelength of one of the two FBGs while the other one keeps unchanged, the fiber laser keeps stable dual-wavelength lasing and the linewidth is still ~700 Hz. It can be seen that the compression for the linewidth based on the Rayleigh backscattering can be used in multi-wavelength laser systems, and because of the characteristic of the Rayleigh backscattering, the method has great potential in the application of wide wavelength range linewidth compression from the ultraviolet to the far infrared.

Biomedical applications of the graphene-based materials.

Graphene, a rapidly rising star, has gained extensive research interests lately due to its excellent properties--such as the exceptional optical, electrical, thermal and mechanical features--which are superior to other materials, so it is called "two-dimensional magical materials". This article presents diverse types and various properties of graphene-based materials, and the current methods for the surface modifications of the graphene-based materials are briefly described. In addition, the in vivo and in vitro cytotoxicity of graphene-based materials are comprehensively discussed. What's more, a summary of its biomedical applications such as drug/gene delivery, photothermal therapy, photodynamic therapy and multimodality therapy is also offered. Finally, an outlook of the graphene-based materials and the challenges in this field are briefly discussed.

Evaluation in vitro and in vivo of curcumin-loaded mPEG-PLA/TPGS mixed micelles for oral administration.

The aim of this work is to prepare and characterize curcumin-loaded methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelles (CUR-MPP-TPGS-MMs), analyze the influence of formulation on enhancing the solubility of curcumin in water, and evaluate the improvement of intestinal absorption after oral administration. CUR-MPP-TPGS-MMs were prepared using the thin film diffusion method and optimized with the uniform design. The optimal CUR-MPP-TPGS-MMs were provided with high drug-loading (16.1%), small size (46.0 nm) and spherical shape. Low critical micelle concentration (CMC) and superior dilution stability showed that CUR-MPP-TPGS-MMs could keep integrity during the dilution of gastrointestinal fluid. In vitro drug release study indicated a sustained release of curcumin from CUR-MPP-TPGS-MMs in simulated gastrointestinal solution. The absorption mechanism of passive diffusion was obtained by measuring in situ intestinal absorption of CUR-MPP-TPGS-MMs in rats, and the best absorption segment was found to be the duodenum. The pharmacokinetics was evaluated in rats at the dose of 75 mg/kg by intragastric administration. The Cmax and mean retention time (MRT0-24) for CUR-MPP-TPGS-MMs were both increased, and the relative bioavailability of micelle formulation to curcumin suspension was 927.3%. These results suggested that mPEG-PLA/TPGS mixed micelle system (MPP-TPGS-MMs) showed great potential in improving oral bioavailability of curcumin.

Recent progresses in bioadhesive microspheres via transmucosal administration.

Based on the advantages of adhesion preparations and the application status of microspheres (MSs) in mucous delivery, this paper primarily reviews the bioadhesive MSs via transmucosal administration routes, including the mucosa in alimentary tract and other lumens. Particularly, the detailed researches about of celladhesive MSs and some new-style bioadhesive MSs are mentioned. Furthermore, this review attempts to reveal the advances of bioadhesive MSs as cell-selective bioadhesion systems and the stimuli-responsive MSs as location-specific drug delivery systems. Although these MSs show powerful strength, some far-sighted ideas should be brought on agendas. In the future, mechanisms should be put under tight scrutiny and more attention should be focused on the excellent bioadhesive materials and the 'second generation mucoadhesives'. Meaningful clinical applications of these novel MSs are also of current concerns and need more detailed researches.