Jianxun Ding

Self-targetability is an emerging targeting strategy for polymer nanocarriers with facile preparation and high targeting efficiency. An acid-sensitive dextran-doxorubicin prodrug (Dex-g-DOX) has been synthesized and used as a self-targeted drug delivery system for the treatment of orthotopic hepatoma. The polysaccharide prodrug exhibits ultraselective accumulation in cancerous liver tissue, acid-sensitive DOX release within cells, and high antitumor efficacy in vitro and in vivo. Therefore, Dex-g-DOX demonstrates great potential for chemotherapy of orthotopic hepatoma.

Recently, chemotherapy has been one of the most important therapeutic approaches for malignant tumors. The tumor tissular or intracellular microenvironment-sensitive polymer-doxorubicin (DOX) conjugates demonstrate great potential for improved antitumor efficacy and reduced side effects. In this work, the acid-sensitive dextran-DOX conjugate (noted as Dex-O-DOX) was synthesized through the versatile efficient oximation reaction between the terminal aldehyde group of polysaccharide and the amino group in DOX in the buffer solution of sodium acetate/acetic acid. The insensitive one, i.e., Dex-b-DOX, was prepared similarly as Dex-O-DOX with a supplemented reduction reaction. The DOX release from Dex-O-DOX was pH-dependent and accelerated by the decreased pH. The efficient intracellular DOX release from Dex-O-DOX toward the human hepatoma HepG2 cells was further confirmed. Furthermore, Dex-O-DOX exhibited a closer antiproliferative activity to free DOX·HCl as the extension of time. More...

The reduction-responsive polymeric nanocarriers have attracted considerable interest because of a significantly higher concentration of intracellular glutathione in comparison with that outside cells. The smart nanovehicles can selectively transport the antitumor drugs into cells to improve efficacies and decrease side effects. In this work, a facilely prepared glutathione-degradable nanogel was employed for targeting intracellular delivery of an antitumor drug (ie, doxorubicin [DOX]). DOX was loaded into nanogel through a sequential dispersion and dialysis approach with a drug loading efficiency of 56.8 wt%, and the laden nanogel (noted as NG/DOX) showed an appropriate hydrodynamic radius of 56.1±3.5 nm. NG/DOX exhibited enhanced or improved maximum tolerated dose on healthy Kunming mice and enhanced intratumoral accumulation and dose-dependent antitumor efficacy toward H22 hepatoma-xenografted mouse model compared with free drug. In addition, the upregulated antitumor efficacy of ...

Apart from the immunosuppressive property, which has been widely investigated in the treatment of various autoimmune diseases, bone marrow mesenchymal stem cells (BMMSCs) also exhibit the chondrogenic capacity. Recently, BMMSCs have attracted more and more attention in the remission of rheumatoid arthritis (RA) and the reconstruction of cartilage injury. In addition to the significant regulatory hurdles of systemic treatment by BMMSCs, the poor inhibitory efficiency on articular inflammatory reaction and the inferior result of preventing the persistent destruction of cartilage were observed. Herein, toward the ovalbumin (OVA)-induced arthritis in rabbits, the in situ transplantation of fibrin gel-encapsulated BMMSCs to osteochondral defect was confirmed to result in the decreased levels of cytokines, such as interleukin-1β, interleukin-6, tumor necrosis factor-α, and anti-OVA antibody, in the serum. What is more, the implantation of BMMSCs also inhibited the proliferation of antigen...

A new multiresolution (MR) preconditioner is presented in this paper, and it is combined with the multilevel fast multipole algorithm (MLFMA) for the analysis of electromagnetic scatters; Furthermore, the MR preconditioner is modified to be more effective by including a perturbation which is constructed from the principle value term of the magnetic field integral equation (MFIE) operator for solving the

Copyright 1997 IEEE. Published in the Proceedings of the Third International Symposium on High Performance Computer Architecture, February 1-5, 1997 in San Antonio, Texas, USA. Personal use of this material is permitted. However, permission to reprint/republish this material for ...

Self-healing polymeric hydrogels have the capability to recover their structures and functionalities upon injury, which are extremely attractive in emerging biomedical applications. This research reports a new kind of self-healing polypeptide hydrogels based on self-assembly between cholesterol (Chol)-modified triblock poly(l-glutamic acid)-block-poly(ethylene glycol)-block-poly(l-glutamic acid) ((PLGA-b-PEG-b-PLGA)-g-Chol) and β-cyclodextrin (β-CD)-modified poly(l-glutamic acid) (PLGA-g-β-CD). The hydrogel formation relied on the host and guest linkage between β-CD and Chol. This study demonstrates the influences of polymer concentration and β-CD/Chol molar ratio on viscoelastic behavior of the hydrogels. The results showed that storage modulus was highest at polymer concentration of 15% w/v and β-CD/Chol molar ratio of 1:1. The effect of the PLGA molecular weight in (PLGA-b-PEG-b-PLGA)-g-Chol on viscoelastic behavior, mechanical properties and in vitro degradation of the supramole...

ABSTRACT Complications arising from tendon injury include tendon sheath infection and peritendinous adhesion, in which tendon adhesion often leads to serious motor dysfunction. In this work, the electrospun membranes of poly(L-lactide) (PLA) and poly(ε-caprolactone) (PCL) with different degradation kinetics were used to investigate their efficacy for anti-adhesion toward Achilles tendon repair. Compared with the PCL membrane, the PLA sample showed a faster rate of degradation in 42 d, and all the degradation media (i.e., phosphate-buffered saline) maintained at a constant pH of around 7.4. Meanwhile, the superior biocompatibility of both the PLA and PCL membranes were proved by the in vitro cellular adhesion tests and in vivo histopathological assays. Simultaneously, the PLA membrane was more effective than the PCL sample in decreasing adhesion and promoting functional recovery. Furthermore, the experiment result was further confirmed by hematoxylin-eosin and Masson’s trichrome staining, and type I collagen immunohistochemical analysis. All results revealed that the model treated with the electrospun PLA membrane was obviously better with regard to both anti-adhesion and tendon repair than that in the PCL membrane group. Considering the results of degradation and adhesion prevention efficacy, the electrospun polyester membranes, especially the PLA one, would be applied with fascinating potential in clinical prevention of postoperative tendon adhesion.

Benefited from the high orientation of coordinated interaction, metallo-supramolecular materials have attracted enormous interests in many fields. Herein, a novel metallo-supramolecular nanogel (SNG)-based drug delivery system for synergistic chemo-photodynamic therapy is explored to enhance anticancer efficacy. It is fabricated by the metallo-supramolecular-coordinated interaction between tetraphenylporphyrin zinc (Zn-Por) and histidine. It can respond to tumor acid microenvironment to release the co-delivered anticancer drug and photosensitizer to kill the lesion cells. Zn-Por moieties in SNG keep the photosensitivity in the range of visible wavelength and possess the ability of generating active oxygen species for photodynamic therapy. The drug-loaded SNG provides a di-functional platform for chemotherapy and photodynamic therapy. Compared with the single chemotherapy of free doxorubicine (DOX) or photodynamic therapy of Zn-Por in SNG, DOX-loaded SNG with irradiation shows higher...

Mesenchymal stem cells (MSCs) are an attractive source for the clinical cell therapy of liver injury. Although the use of adult serum, platelet lysate, or cord blood serum solves some of the problems caused by fetal bovine serum (FBS), the allogeneic immune response, contamination, and donor-to-donor and donor-to-receptor differences still obstruct the application of MSCs. In this study, the influences of autoserum from liver-injured rats (LIRs) and allogeneic serum from healthy rats on the isolation and culture of bone marrow MSCs (BMSCs) were examined and compared to FBS. The results showed that BMSCs cultured with autoserum or allogeneic serum exhibited better MSC-specific morphology, lower rate of cell senescent, and higher proliferation kinetics than those with FBS. In addition, autoserum promoted the osteogenic differentiation potential of BMSCs as allogeneic serum did. Although there were no significant differences in proliferation activity, immunophenotypic characterization,...

In this paper, we propose an adaptive scan (AS) strategy for submesh allocation. The earlier frame sliding (FS) strategy allocates submeshes based on fixed orientations of incoming faska. It also slides fiunaes om mesh planes by fdzed strides. Our AS a1Iocation strategy differs from the FS strategy in the following two ways: (1) it does not fiz the orientations of

The persistent inflammation of rheumatoid arthritis (RA) always leads to partial synovial hyperplasia and the destruction of articular cartilage. Bone marrow mesenchymal stem cells (BMMSCs) have been proven to possess immunosuppressive effects, and widely explored in the treatment of autoimmune diseases. However, poor inhibitory effect on local inflammatory state and limited capacity of preventing destruction of articular cartilage by systemic BMMSCs transplantation were observed. Herein, toward the classical type II collagen-induced arthritis in rats, the combination treatment of microfracture and in situ transplantation of thermogel-encapsulated BMMSCs was verified to obviously down-regulate the ratio of CD4+ to CD8+ T lymphocytes in peripheral blood. In addition, it resulted in the decreased levels of inflammatory cytokines, such as interleukin-1β, tumor necrosis factor-α and anti-collagen type II antibody, in the serum. Simultaneously, the combination therapy also could inhibit ...

A reversible PEGylated prodrug integrates the advantages of PEGylation and responsiveness. J. Ding and colleagues reveal on page 844 that the prodrug exhibits acid-accelerated drug release, improved cellular internalization and cytotoxicity in vitro, and upregulated intratumoral accumulation, antitumor efficacy, and security in vivo.

A tubular poly(ε-caprolactone) (PCL)/poly(lactide-co-glycolide) (PLGA) ureteral stent composed of nanofibers with micropores was fabricated by double-needle electrospinning. The stent was ureteroscopically inserted into six Changbai pigs, and the commercial polyurethane Shagong(®) stent was inserted into four pigs as control. Intravenous pyelography revealed that the PCL/PLGA stent gradually degraded from the distal end to proximal terminal, and all stents were completely degraded at 10 weeks post-insertion. No significant difference was observed in hydronephrosis severity between the two groups. The levels of serum creatinine and urine pH remained similar throughout the study in the two groups, but the number of white blood cells in the urine was significantly higher in the Shagong(®) stent group. On Day 70, histological evaluation indicated equivalent histological severity scores in the middle and distal ureter sections and bladder in the two groups. However, the PCL/PLGA stent-implanted pigs had significantly lower mean severity scores in the kidney and proximal ureter sites. These data revealed that the PCL/PLGA stent degraded in a controlled manner, did not induce obstruction, and had a lower urothelial impact in comparison to the Shagong(®) stent, indicating that the stent exhibited great potential for clinical application.

RNA interference (RNAi) provides the promising treatments of gene-related diseases while hindered by the lack of highly efficient delivery platform with low cytotoxicity. Moreover, the intracellular fates of nonviral gene carriers are closely related to their internalization pathway, and eventually influence their RNAi efficiency. Herein, a series of guanidinated thiourea-modified polyethylenimines (PEI-MTU-Gs) are synthesized and utilized as the efficient carriers of small interfering RNA (siRNA) with up to 71.6% inhibition of luciferase activity in the luciferase-expressing cell lines (i.e., HeLa/Luc cells). The introduction of noncationic hydrogen bond donors, that is, thiourea groups, provides the carriers with much lower cytotoxicities and relatively looser complex structures that facilitate the intracellular release of siRNAs. Furthermore, the multiguanidino structures endow the PEI-MTU-G/siRNA complexes with the ability to directly penetrate cell membrane, which facilitates t...

An acid-labile dextran-bortezomib conjugate (Dex-BTZ), i.e., a macromolecularized proteasome inhibitor, is synthesized by a boron esterification reaction. The prodrug exhibits intracellular acidity-accelerated BTZ release, and up-regulated inhibition efficacies toward hypoxic tumor in vitro and in vivo through both NF-κB- and ERS-mediated apoptosis signaling pathways.

Two pH-activatable star-shaped prodrugs are synthesized through the condensation reaction between Y- or dumbbell-shaped poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PEG-PLGA) copolymer and acid-sensitive cis-aconityl-doxorubicin. The prodrugs self-assemble into micelles with favorable hydrodynamic radii and relatively low critical micelle concentrations. In vitro DOX release from prodrug micelles is accelerated by the decrease of the PLGA content or at the late endosomal pH. The efficient cellular uptake and intracellular DOX release of the prodrug micelles are confirmed and the improved long-term anti-proliferative activities of prodrug micelles are revealed. These features suggest that the prodrugs provide a favorable approach to construct effective polymeric drug delivery systems for malignancy therapy.

The amphiphilic diblock copolymer composed of methoxy poly(ethylene glycol) and racemic oligoleucine was synthesized which formed into micelle with uniform size in aqueous environment. Doxorubicin (DOX) was loaded into micelle aided by noncovalent interactions with high drug loading efficiency. The DOX-loaded micelle (referred as M-DOX) demonstrated the sustained drug release in vitro and excellent antiproliferative capability toward both MG63 and Saos-2 cells. Furthermore, for both MG63 and Saos-2-xenografted BALB/c nude mouse models, M-DOX exhibited enhanced intratumoral distribution, improved antitumor efficacy, and reduced side effects compared with free DOX. Therefore, the polypeptide micelle showed a bright prospect for controlled delivery of antitumor drugs in vivo.

Back Cover: On page 328 J. Ding, J. Wang, and co-workers present a doxorubicin-loaded polypeptide micelle with suitable uniform size, high loading efficiency, and durable release. The laden micelle selectively accumulates in tumor tissue and effectively inhibits the growth of osteosarcoma with improved security in vivo.

Cisco systems' application oriented networking (AON) is an important network element towards building next generation service oriented network. AON processes application- level content and moves far beyond a conventional content-aware Web switch. It creates a novel content delivery platform and allows more sophisticated message-level load balancing mechanisms to be deployed in a switch/router in front of back-end servers. In addition

In the past few decades, the in situ sustained drug delivery platforms present fascinating potential in sentinel chemotherapy of various solid tumors. In this work, doxorubicin (DOX), a model antitumor drug, was loaded into the thermogel of poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide). The moderate mechanical property of DOX-loaded hydrogel was confirmed by rheological test. In vitro degradation revealed the good biodegradability of thermogel. The DOX-loaded hydrogel exhibited the sustained release profiles up to 30days without and even with elastase. The improved in vivo tumor inhibition and reduced side-effects were observed in the DOX-incorporated hydrogel group compared with those in free DOX group. The excellent in vivo results were further confirmed by the histopathological evaluation or terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The thermogel with great prospect may be used as an ideal controlled dru...

For efficiently solving large dense complex linear systems with multiple right-hand sides that arise in monostatic radar cross section (RCS) calculation, a spectral multiresolution method combined with the multilevel fast multipole algorithm (MLFMA) is developed and used in the context of the generalized minimal residual iterative method (GMRES). In this scheme, the MLFMA is used to speed up the matrix

The formation of Diamond-Like Carbon (DLC) structure on the surface of Highly Oriented Pyrolytic Graphite (HOPG) following Xeq+ (q=5∼26) ions irradiation with different fluence is studied with Raman and X-ray photoelectron spectroscopy (XPS) analyses in this work. The DLC structure formed on HOPG is shown by the electronic structure transition from sp2 to sp3 hybridization. An obvious evolution of the

Two kinds of triblock poly(ethylene glycol)-polyleucine (PEG-PLeu) copolymers were synthesized through the ring-opening polymerization of L-Leu N-carboxyanhydride (NCA), or equivalent D-Leu NCA and L-Leu NCA with amino-terminated PEG as a macroinitiator. The amphiphilic copolymers spontaneously self-assembled into spherical micellar aggregations in an aqueous environment. The micelle with a racemic polypeptide core exhibited smaller critical micelle concentration and diameter compared to those with a levorotatory polypeptide core. A model anthracycline antineoplastic agent, i.e., doxorubicin (DOX), was loaded into micelles through nanoprecipitation, and the PEG-P(D,L-Leu) micelle exhibited higher drug-loading efficacy than that with a P(L-Leu) core-this difference was attributed to the flexible and compact P(L-Leu) core. Sustained in vitro DOX release from micelles with both levorotatory and racemic polypeptide cores was observed, and the DOX-loaded PEG-P(D,L-Leu) micelle exhibited ...

Cisco Systems application oriented networking (AON) product is an important network element towards building next generation service oriented intelligent information network (IIN). AON processes application-level content and moves far beyond a conventional content-aware Web switch. It creates a novel content delivery platform and allows more sophisticated load balancing schemes to be deployed in a switch among back-end servers to reduce

Spinal cord injury (SCI) is a devastating event that causes substantial morbidity and mortality, for which no fully restorative treatments are available. Stem cells transplantation offers some promise in the restoration of neurological function but with limitations. Insulin-like growth factor 1 (IGF-1) is a well-appreciated neuroprotective factor that is involved with various aspects of neural cells. Herein, the IGF-1 gene was introduced into spinal cord-derived neural stem cells (NSCs) and expressed steadily. The IGF-1-transfected NSCs exhibited higher viability and were promoted to differentiate into oligodendrocytes. Moreover, the most possible underlying mechanism, through which IGF-1 exerted its neuroprotective effects, was investigated. The result revealed that the differentiation was mediated by the IGF-1 activated extracellular signal-regulated kinases 1 and 2 (ERK1/2) and its downstream pathway. These findings provide the evidence for revealing the therapeutic merits of IGF...