Off‐Stoichiometric Thiol‐Ene Chemistry to Dendritic Nanogel Therapeutics

A novel platform of dendritic nanogels is herein presented, capitalizing on the self‐assembly of allyl‐functional polyesters based on dendritic‐linear‐dendritic amphiphiles followed by simple cross‐linking with complementary monomeric thiols via UV initiated off‐stoichiometric thiol‐ene chemistry. The facile approach enabled multigram creation of allyl reactive nanogel precursors, in the size range of 190–295 nm, being readily available for further modifications to display a number of core functionalities while maintaining the size distribution and characteristics of the master batch. The nanogels are evaluated as carriers of a spread of chemotherapeutics by customizing the core to accommodate each individual cargo. The resulting nanogels are biocompatible, displaying diffusion controlled release of cargo, maintained therapeutic efficacy, and decreased cargo toxic side effects. Finally, the nanogels are found to successfully deliver pharmaceuticals into a 3D pancreatic spheroids tumor model.     

Nanogel Encapsulated Hydrogels As Advanced Wound Dressings for the Controlled Delivery of Antibiotics

Biocompatible and degradable dual-delivery gel systems based on hyperbranched dendritic−linear−dendritic copolymers (HBDLDs) is herein conceptualized and accomplished via thiol-ene click chemistry. The elasticity of the hydrogels is tunable by varying the lengths of PEG (2, 6, 10 kDa) or the dry weight percentages (20, 30, 40 wt%), and are found to range from 2–14.7 kPa, comparable to human skin. The co-delivery of antibiotics is achieved, where the hydrophilic drug novobiocin sodium salt (NB) is entrapped within the hydrophilic hydrogel, while the hydrophobic antibiotic ciprofloxacin (CIP) is encapsulated within the dendritic nanogels (DNGs) with hydrophobic cores (DNGs-CIP). The DNGs-CIP with drug loading capacity of 2.83 wt% are then physically entrapped within the hybrid hydrogels through UV curing. The hybrid hydrogels enable the quick release of NB and prolonged released of CIP. In vitro cell infection assays showed that the antibiotic-loaded hybrid hydrogels are able to treat bacterial infections with significant bacterial reduction. Hybrid hydrogel band aids are fabricated and exhibited better antibacterial activity compared with commercial antimicrobial band aids. Remarkably, most hydrogels and hybrid hydrogels show enhanced human dermal cell proliferation and could be degraded into non-toxic constituents, showing great promise as wound dressing materials.     

Surface Engineered Carboxymethylchitosan/Poly(amidoamine) Dendrimer Nanoparticles for Intracellular Targeting

Novel highly branched biodegradable macromolecular systems have been developed by grafting carboxymethylchitosan (CMCht) onto low generation poly(amidoamine) (PAMAM) dendrimers. Such structures organize into sphere‐like nanoparticles that are proposed to be used as carriers to deliver bioactive molecules aimed at controlling the behavior of stem cells, namely their proliferation and differentiation. The nanoparticles did not exhibit significant cytotoxicity in the range of concentrations below 1 mg mL^?1, and fluorescent probe labeled nanoparticles were found to be internalized with highly efficiency by both human osteoblast‐like cells and rat bone marrow stromal cells, under fluorescence‐activated cell sorting and fluorescence microscopy analyses. Dexamethasone (Dex) has been incorporated into CMCht/PAMAM dendrimer nanoparticles and release rates were determined by high performance liquid chromatography. Moreover, the biochemical data demonstrates that the Dex‐loaded CMCht/PAMAM dendrimer nanoparticles promote the osteogenic differentiation of rat bone marrow stromal cells, in vitro. The nanoparticles exhibit interesting physicochemical and biological properties and have great potential to be used in fundamental cell biology studies as well as in a variety of biomedical applications, including tissue engineering and regenerative medicine.     

Multifunctional Up‐Converting Nanocomposites with Smart Polymer Brushes Gated Mesopores for Cell Imaging and Thermo/pH Dual‐Responsive Drug Controlled Release

Multifunctional nanocarriers based on the up‐conversion luminescent nanoparticles of NaYF₄:Yb³⁺/Er³⁺ core (UCNPs) and thermo/pH‐coupling sensitive polymer poly[(N‐isopropylacrylamide)‐co‐(methacrylic acid)] (P(NIPAm‐co‐MAA)) gated mesoporous silica shell are reported for cancer theranostics, including fluorescence imaging, and for controlled drug release for therapy. The as‐synthesized hybrid nanospheres UCNPs@mSiO₂‐P(NIPAm‐co‐MAA) show bright green up‐conversion fluorescence under 980 nm laser excitation and the thermo/pH‐sensitive polymer is active as a “valve” to moderate the diffusion of the embedded drugs in‐and‐out of the pore channels of the silica container. The anticancer drug doxorubicin hydrochloride (DOX) can be absorbed into UCNPs@mSiO₂‐P(NIPAm‐co‐MAA) nanospheres and the composite drug delivery system (DDS) shows a low level of leakage at low temperature/high pH values but significantly enhanced release at higher temperature/lower pH values, exhibiting an apparent thermo/pH controlled “on‐off” drug release pattern. The as‐prepared UCNPs@mSiO₂‐P(NIPAm‐co‐MAA) hybrid nanospheres can be used as bioimaging agents and biomonitors to track the extent of drug release. The reported multifunctional nanocarriers represent a novel and versatile class of platform for simultaneous imaging and stimuli‐responsive controlled drug delivery.     

Electrospun Fibrous Architectures for Drug Delivery,Tissue Engineering and Cancer Therapy

The versatile electrospinning technique is recognized as an efficient strategy to deliver active pharmaceutical ingredients and has gained tremendous progress in drug delivery, tissue engineering, cancer therapy, and disease diagnosis. Numerous drug delivery systems fabricated through electrospinning regarding the carrier compositions, drug incorporation techniques, release kinetics, and the subsequent therapeutic efficacy are presented herein. Targeting for distinct applications, the composition of drug carriers vary from natural/synthetic polymers/blends, inorganic materials, and even hybrids. Various drug incorporation approaches through electrospinning are thoroughly discussed with respect to the principles, benefits, and limitations. To meet the various requirements in actual sophisticated in vivo environments and to overcome the limitations of a single carrier system, feasible combinations of multiple drug‐inclusion processes via electrospinning could be employed to achieve programmed, multi‐staged, or stimuli‐triggered release of multiple drugs. The therapeutic efficacy of the designed electrospun drug‐eluting systems is further verified in multiple biomedical applications and is comprehensively overviewed, demonstrating promising potential to address a variety of clinical challenges.     

Multifunctional Mesoporous Silica Nanoparticles for Cancer‐Targeted and Controlled Drug Delivery

Multifunctional mesoporous silica nanoparticles are developed in order to deliver anticancer drugs to specific cancer cells in a targeted and controlled manner. The nanoparticle surface is functionalized with amino‐β‐cyclodextrin rings bridged by cleavable disulfide bonds, blocking drugs inside the mesopores of the nanoparticles. Poly(ethylene glycol) polymers, functionalized with an adamantane unit at one end and a folate unit at the other end, are immobilized onto the nanoparticle surface through strong β‐cyclodextrin/adamantane complexation. The non‐cytotoxic nanoparticles containing the folate targeting units are efficiently trapped by folate‐receptor‐rich HeLa cancer cells through receptormmediated endocytosis, while folate‐receptor‐poor human embryonic kidney 293 normal cells show much lower endocytosis towards nanoparticles under the same conditions. The nanoparticles endocytosed by the cancer cells can release loaded doxorubicin into the cells triggered by acidic endosomal pH. After the nanoparticles escape from the endosome and enter into the cytoplasm of cancer cells, the high concentration of glutathione in the cytoplasm can lead to the removal of the β‐cyclodextrin capping rings by cleaving the pre‐installed disulfide bonds, further promoting the release of doxorubicin from the drug carriers. The high drug‐delivery efficacy of the multifunctional nanoparticles is attributed to the co‐operative effects of folate‐mediated targeting and stimuli‐triggered drug release. The present delivery system capable of delivering drugs in a targeted and controlled manner provides a novel platform for the next generation of therapeutics.     

Photo‐ and pH‐Triggered Release of Anticancer Drugs from Mesoporous Silica‐Coated Pd@Ag Nanoparticles

A smart drug delivery system integrating both photothermal therapy and chemotherapy for killing cancer cells is reported. The delivery system is based on a mesoporous silica‐coated Pd@Ag nanoplates composite. The Pd@Ag nanoplate core can effectively absorb and convert near infrared (NIR) light into heat. The mesoporous silica shell is provided as the host for loading anticancer drug, doxorubicin (DOX). The mesoporous shell consists of large pores, ～10 nm in diameter, and allows the DOX loading as high as 49% in weight. DOX loaded core–shell nanoparticles exhibit a higher efficiency in killing cancer cells than free DOX. More importantly, DOX molecules are loaded in the mesopores shell through coordination bonds that are responsive to pH and heat. The release of DOX from the core‐shell delivery vehicles into cancer cells can be therefore triggered by the pH drop caused by endocytosis and also NIR irradiation. A synergistic effect of combining chemotherapy and photothermal therapy is observed in our core‐shell drug delivery system. The cell‐killing efficacy by DOX‐loaded core–shell particles under NIR irradiation is higher than the sum of chemotherapy by DOX‐loaded particles and photothermal therapy by core–shell particles without DOX.     

Multicast‐aware power allocation in multiple spot‐beam satellite communication systems

In this paper, we address the problem of user heterogeneity in satellite multicast from the perspective of resource allocation in a multiple spot‐beam satellite system that supports both unicast and multicast flows. Satellite communication systems, with their wide‐area coverage and direct access to large number of users, clearly have an inherent advantage in supporting multicast applications. In order to remain competitive against other broadband technologies, however, next generation satellite systems will be required to support both unicast and multicast flows and offer optimal sharing of system resources between these flows. We show that user heterogeneity across spot‐beam queues may result in lower allocated session rates for active flows, and be perceived as unsatisfactory by potential users when both unicast and multicast flows are active in the system. We propose an optimization‐based approach that allocates resources with the goal of smoothing user heterogeneity, and show that resulting session rates are higher on the average for both unicast and multicast flows. This is achieved through the re‐distribution of system power among spot‐beam queues, by taking into account the load on the queues and the channel states. We conclude that it is possible to increase the average session rates of multicast flows by 25–100%, and the rates of unicast flows by 15–40% compared to the pre‐optimization levels. Copyright © 2006 John Wiley & Sons, Ltd.     

Antimicrobial Gallium‐Doped Phosphate‐Based Glasses

Novel quaternary gallium‐doped phosphate‐based glasses (1, 3, and 5 mol % Ga₂O₃) were synthesized using a conventional melt quenching technique. The bactericidal activities of the glasses were tested against both Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) and Gram‐positive (Staphylococcus aureus, methicillin‐resistant Staphylococcus aureus, and Clostridium difficile) bacteria. Results of the solubility and ion release studies showed that these glass systems are unique for controlled delivery of Ga³⁺. ⁷¹Ga NMR measurements showed that the gallium is mostly octahedrally coordinated by oxygen atoms, whilst FTIR spectroscopy provided evidence for the presence of a small proportion of tetrahedral gallium in the samples with the highest gallium content. FTIR and Raman spectra also afford an insight into the correlation between the structure and the observed dissolution behavior via an understanding of the atomic‐scale network bonding characteristics. The results confirmed that the net bactericidal effect was due to Ga³⁺, and a concentration as low as 1 mol % Ga₂O₃ was sufficient to mount a potent antibacterial effect. The dearth of new antibiotics in development makes Ga³⁺ a potentially promising new therapeutic agent for pathogenic bacteria including MRSA and C. difficile.     

Design and Analysis of Optimal Multi-Level Hierarchical Mobile IPv6 Networks

Hierarchical Mobile IPv6 (HMIPv6) is an enhanced version of Mobile IPv6 designed to reduce signaling overhead and to support seamless handoff in IP-based wireless/mobile networks. To support more scalable services, HMIPv6 networks can be organized as the form of a multi-level hierarchy architecture (i.e., tree structure). However, since multi-level HMIPv6 networks incur additional packet processing overhead at multiple mobility agents, it is important to find the optimal hierarchy level to minimize the total cost, which consists of the location update cost and the packet delivery cost. In this paper, we investigate this problem, namely the design of an optimal multi-level HMIPv6 (OM-HMIPv6) network. To accomplish this, we design a function to represent the location update cost and the packet delivery cost in multi-level HMIPv6 networks. Based on these formulated cost functions, we calculate the optimal hierarchy level in multi-level HMIPv6 networks, in order to minimize the total cost. In addition, we investigate the effects of the session-to-mobility ratio (SMR) on the total cost and the optimal hierarchy. The numerical results, which show various relationships among the network size, optimal hierarchy, and SMR, can be utilized to design an optimal HMIPv6 network. In addition, the analytical results are validated by comprehensive simulations. Sangheon Pack received his B.S. (2000, magna cum laude) and Ph.D. (2005) degrees from Seoul National University, both in computer engineering. He is a post doctor fellow in the School of Computer Science and Engineering at the Seoul National University, Korea. He is a member of the IEEE and ACM. During 2002–2005, he was a recipient of the Korea Foundation for Advanced Studies (KFAS) Computer Science and Information Technology Scholarship. He has been also a member of Samsung Frontier Membership (SFM) from 1999. He received a student travel grant award for the IFIP Personal Wireless Conference (PWC) 2003. He was a visiting researcher to Fraunhofer FOKUS, German in 2003. His research interests include mobility management, wireless multimedia transmission, and QoS provision issues in the next-generation wireless/mobile networks. Yanghee Choi received B.S. in electronics engineering from Seoul National University, M.S. in electrical engineering from Korea advanced Institute of Science, and Doctor of Engineering in Computer Science from Ecole Nationale Superieure des Telecommunications (ENST) in Paris, in 1975, 1977 and 1984 respectively. Before joining the School of Computer Engineering, Seoul National University in 1991, he has been with Electronics and Telecommunications Research Institute (ETRI) during 1977–1991, where he served as director of Data Communication Section, and Protocol Engineering Center. He was research student at Centre National d'Etude des Telecommunications (CNET), Issy-les-Moulineaux, during 1981–1984. He was also Visiting Scientist to IBM T.J. Watson Research Center for the year 1988–1989. He is now leading the Multimedia Communications Laboratory in Seoul National University. He is also director of Computer Network Research Center in Institute of Computer Technology (ICT). He was editor-in-chief of Korea Information Science Society journals. He was chairman of the Special Interest Group on Information Networking. He has been associate dean of research affairs at Seoul National University. He was president of Open Systems and Internet Association of Korea. His research interest lies in the field of multimedia systems and high-speed networking. Minji Nam received her B.S. and M.S degrees in Computer Science and Engineering from Seoul National University in 2003 and 2005, respectively. From 2005, she has worked on Portable Internet Development Team for Korea Telecom. Her research interests are mobile networks, portable internet technology (IEEE 802.16) and Mobile IPv6.