Advanced Healthcare Materials

Cover image for Vol. 3 Issue 8

Special Issue: Advanced Drug Delivery Systems for Therapeutic Applications

August, 2014

Volume 3, Issue 8

Pages 1121–1343

  1. Cover Picture

    1. Top of page
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    3. Inside Front Cover
    4. Back Cover
    5. Masthead
    6. Contents
    7. Editorial
    8. Progress Reports
    9. Reviews
    10. Communications
    11. Full Papers
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      Drug Delivery: Enzyme-Responsive Cell-Penetrating Peptide Conjugated Mesoporous Silica Quantum Dot Nanocarriers for Controlled Release of Nucleus-Targeted Drug Molecules and Real-Time Intracellular Fluorescence Imaging of Tumor Cells (Adv. Healthcare Mater. 8/2014) (page 1121)

      Jinming Li, Fang Liu, Qing Shao, Yuanzeng Min, Marianne Costa, Edwin K. L. Yeow and Bengang Xing

      Version of Record online: 14 AUG 2014 | DOI: 10.1002/adhm.201470038

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      On page 1230, B. Xing, E. K. L. Yeow, and co-workers present a specific tumor microenvironment-responsive silica quantum dot nano-platform where potent antitumor reagents are loaded onto the surface of enzyme activatable cell penetrating peptide conjugated nanoparticles. This personalized nanomedicine platform can be specifically recognized by enzymes found only over-expressed in the tumor cell environment that can selectively control the localized drug release into the nucleus of targeted tumor cells, eliciting significant tumor cytotoxicity with minimum side effects. This platform also provides real-time imaging of the tumor targeting process and intracellular drug delivery.

  2. Inside Front Cover

    1. Top of page
    2. Cover Picture
    3. Inside Front Cover
    4. Back Cover
    5. Masthead
    6. Contents
    7. Editorial
    8. Progress Reports
    9. Reviews
    10. Communications
    11. Full Papers
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      Phototherapy: Targeting-Triggered Porphysome Nanostructure Disruption for Activatable Photodynamic Therapy (Adv. Healthcare Mater. 8/2014) (page 1122)

      Cheng S. Jin, Liyang Cui, Fan Wang, Juan Chen and Gang Zheng

      Version of Record online: 14 AUG 2014 | DOI: 10.1002/adhm.201470039

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      Porphysome is the most stable and efficient delivery system of porphyrins, but the nanostructure converts the singlet oxygen generation mechanism to a thermal ablation mechanism. On page 1240, by incorporating targeting ligands (e.g. folate) into porphysome formulation, G. Zheng, J. Chen, and co-workers show that receptor-mediated endocytosis facilitates the nanostructure disruption inside cells, which switches back on singlet oxygen generation of the densely packed porphyrins for effective photodynamic therapy (PDT).

  3. Back Cover

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    3. Inside Front Cover
    4. Back Cover
    5. Masthead
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    7. Editorial
    8. Progress Reports
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    10. Communications
    11. Full Papers
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      Gene Therapy: Carbon-Dot-Based Two-Photon Visible Nanocarriers for Safe and Highly Efficient Delivery of siRNA and DNA (Adv. Healthcare Mater. 8/2014) (page 1348)

      Liqin Wang, Xiaoyong Wang, Ashwinkumar Bhirde, Jianbo Cao, Yun Zeng, Xinglu Huang, Yaping Sun, Gang Liu and Xiaoyuan Chen

      Version of Record online: 14 AUG 2014 | DOI: 10.1002/adhm.201470042

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      X. Chen, G. Liu, and co-workers develop photoluminescent carbon dots (Cdot) by using low molecular weight amphiphilic polyethylenimine for surface passivation, which possesses low cytotoxicity, good stability, monodispersity with narrow size distribution, high gene delivery efficiency, and fluorescence performance. The Cdot formula introduced on page 1203 serves as a novel imaging-trackable gene-delivery na nocarrier promising for gene therapy and optical molecular imaging.

  4. Masthead

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      Masthead: (Adv. Healthcare Mater. 8/2014)

      Version of Record online: 14 AUG 2014 | DOI: 10.1002/adhm.201470041

  5. Contents

    1. Top of page
    2. Cover Picture
    3. Inside Front Cover
    4. Back Cover
    5. Masthead
    6. Contents
    7. Editorial
    8. Progress Reports
    9. Reviews
    10. Communications
    11. Full Papers
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  6. Editorial

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      Advanced Drug Delivery Systems for Therapeutic Applications (pages 1130–1132)

      Hsing-Wen Sung and Zhuang Liu

      Version of Record online: 14 AUG 2014 | DOI: 10.1002/adhm.201400323

  7. Progress Reports

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    10. Communications
    11. Full Papers
    1. Injectable Cell Constructs Fabricated via Culture on a Thermoresponsive Methylcellulose Hydrogel System for the Treatment of Ischemic Diseases (pages 1133–1148)

      Chieh-Cheng Huang, Zi-Xian Liao, Ding-Yuan Chen, Chun-Wen Hsiao, Yen Chang and Hsing-Wen Sung

      Version of Record online: 27 JAN 2014 | DOI: 10.1002/adhm.201300605

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      By employing a thermoresponsive methylcellulose hydrogel system, various injectable cell constructs are fabricated, including cell sheet fragments, cell bodies, core–shell cell bodies, and hypoxic mixed cell bodies, for treating ischemic diseases. This Progress Report discusses in vitro observations and in vivo therapeutic efficacy of each cell construct.

    2. Reactive Oxygen Species-Scavenging Nanomedicines for the Treatment of Oxidative Stress Injuries (pages 1149–1161)

      Toru Yoshitomi and Yukio Nagasaki

      Version of Record online: 30 JAN 2014 | DOI: 10.1002/adhm.201300576

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      Redox polymer therapeutics using nitroxide radical-containig nanoparticles is developed. pH-sensitive RNPN shows remarkable therapeutic effects on ischemia–reperfusion injuries after its intravenous administration. On the contrary, the pH-insensitive RNPO accumulates in the mucosa and inflamed areas of the gastrointestinal tract after oral administration without uptake in blood, resulting in remarkable therapeutic effects on colitis and small intestinal inflammation.

    3. Nanostructural Systems Developed with Positive Charge Generation to Drug Delivery (pages 1162–1181)

      Fei-Fei An, Weipeng Cao and Xing-Jie Liang

      Version of Record online: 18 FEB 2014 | DOI: 10.1002/adhm.201300600

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      Positive-charge-generating nanostructures are highly attractive nanocarriers for efficient drug delivery to tumor due to their combined advantages of long blood circulation, passive tumoral accumulation, stimulus-enhanced cell uptake, and intracellular drug release. This Progress Report discusses the design and application of each type of positive-charge-generating nanostructures to drug delivery.

  8. Reviews

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    7. Editorial
    8. Progress Reports
    9. Reviews
    10. Communications
    11. Full Papers
    1. Tumor-Targeting Multifunctional Nanoparticles for siRNA Delivery: Recent Advances in Cancer Therapy (pages 1182–1193)

      Sook Hee Ku, Kwangmeyung Kim, Kuiwon Choi, Sun Hwa Kim and Ick Chan Kwon

      Version of Record online: 28 FEB 2014 | DOI: 10.1002/adhm.201300607

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      Nanotechnology offers an ideal opportunity to develop the efficient siRNA delivery system for cancer therapy. In this Review, tumor-targeting strategies of nano­particles, passive targeting and active targeting, are summarized. The recent advances in siRNA nanocarriers for cancer treatment, containing multifunctionalities, are also highlighted.

  9. Communications

    1. Top of page
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    9. Reviews
    10. Communications
    11. Full Papers
    1. Gold Nanoparticles Displaying Tumor-Associated Self-Antigens as a Potential Vaccine for Cancer Immunotherapy (pages 1194–1199)

      Sukyung Ahn, In-Hyun Lee, Sukmo Kang, Daejin Kim, Minsuk Choi, Phei Er Saw, Eui-Cheol Shin and Sangyong Jon

      Version of Record online: 20 MAR 2014 | DOI: 10.1002/adhm.201300597

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      Golden vaccine for cancers. Gold nanoparticles enable efficient antigen delivery to dendritic cells and then activate the cells to facilitate cross-presentation, inducing antigen-specific cytotoxic T-lymphocyte responses for effective cancer therapy.

    2. The Role of Surface Functionality in Nanoparticle Exocytosis (pages 1200–1202)

      Chang Soo Kim, Ngoc D. B. Le, Yuqing Xing, Bo Yan, Gulen Yesilbag Tonga, Chaekyu Kim, Richard W. Vachet and Vincent M. Rotello

      Version of Record online: 24 MAR 2014 | DOI: 10.1002/adhm.201400001

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      Getting out is just as important for nano­therapeutics as getting in. Exocytosis rates determine residency time in the cell, an important determinant for therapeutic efficacy and also for eventual clearance from the cell. In this study, it is shown that exocytosis efficiency is determined by surface functionality, providing a strategy for optimizing nanocarriers.

    3. Carbon-Dot-Based Two-Photon Visible Nanocarriers for Safe and Highly Efficient Delivery of siRNA and DNA (pages 1203–1209)

      Liqin Wang, Xiaoyong Wang, Ashwinkumar Bhirde, Jianbo Cao, Yun Zeng, Xinglu Huang, Yaping Sun, Gang Liu and Xiaoyuan Chen

      Version of Record online: 2 APR 2014 | DOI: 10.1002/adhm.201300611

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      A simple and versatile nanoparticulate siRNA and DNA delivery vehicle is reported, based on photonic Cdots by using Alkyl–PEI2k for surface passivation.

    4. Prodrug Strategy to Achieve Lyophilizable, High Drug Loading Micelle Formulations Through Diester Derivatives of β-Lapachone (pages 1210–1216)

      Xinpeng Ma, Xiumei Huang, Gang Huang, Longshan Li, Yiguang Wang, Xiuquan Luo, David A. Boothman and Jinming Gao

      Version of Record online: 14 FEB 2014 | DOI: 10.1002/adhm.201300590

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      β-Lap prodrug micelle strategy improves the formulation properties of β-lap therapeutics. The resulting micelles yield apparent high β-lap solubility (>7 mg mL−1), physical stability, and ability to reconstitute after lyophilization. In the presence of esterase, β-lap prodrugs are efficiently converted into parent drug (i.e., β-lap), resulting in NQO1-dependent lethality of NSCLC cells.

    5. Supramolecular Nanofibrils Inhibit Cancer Progression In Vitro and In Vivo (pages 1217–1221)

      Yi Kuang, Xuewen Du, Jie Zhou and Bing Xu

      Version of Record online: 20 FEB 2014 | DOI: 10.1002/adhm.201300645

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      Self-assembly of small peptide derivatives affords supramolecular nanofibrils that possess characteristic features of amyloid oligomers. Acting as de novo amyloid oligomers, the nanofibrils effectively inhibit the tumor progression both in vitro and in vivo, which demonstrates a new type of anticancer approach and may provide new insights for inverse comorbidity between cancer and neurodegenerative diseases.

    6. Neutralized Nanoparticle Composed of SS-Cleavable and pH-Activated Lipid-Like Material as a Long-Lasting and Liver-Specific Gene Delivery System (pages 1222–1229)

      Masami Ukawa, Hidetaka Akita, Yasuhiro Hayashi, Ryohei Ishiba, Kota Tange, Masaya Arai, Kazuhiro Kubo, Yuriko Higuchi, Kazunori Shimizu, Satoshi Konishi, Mitsuru Hashida and Hideyoshi Harashima

      Version of Record online: 26 MAR 2014 | DOI: 10.1002/adhm.201300629

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      Charge-neutralized lipid envelope-type nanoparticles formed with SS-cleavable and pH-activated lipid-like materials (ssPalm) accumulate rapidly in the liver without forming aggregates in the blood circulation, and result in a liver-specific gene expression for a long duration (>2 weeks) with neither immunological responses nor hepatotoxicity after intraveneous administration, when it carries pDNA free from CpG-motifs.

  10. Full Papers

    1. Top of page
    2. Cover Picture
    3. Inside Front Cover
    4. Back Cover
    5. Masthead
    6. Contents
    7. Editorial
    8. Progress Reports
    9. Reviews
    10. Communications
    11. Full Papers
    1. Enzyme-Responsive Cell-Penetrating Peptide Conjugated Mesoporous Silica Quantum Dot Nanocarriers for Controlled Release of Nucleus-Targeted Drug Molecules and Real-Time Intracellular Fluorescence Imaging of Tumor Cells (pages 1230–1239)

      Jinming Li, Fang Liu, Qing Shao, Yuanzeng Min, Marianne Costa, Edwin K. L. Yeow and Bengang Xing

      Version of Record online: 18 FEB 2014 | DOI: 10.1002/adhm.201300613

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      A set of mesoporous silica (mSiO 2 )-coated quantum dot (QD) nanocarriers functionalized with an enzyme-responsive cell-penetrating peptide sequence is presented to control the targeted delivery of antitumor reagent, doxorubicin (DOX) into the nucleus of tumor cells, and meantime to real-time image the targeting and delivery through QD fluorescence.

    2. Targeting-Triggered Porphysome Nanostructure Disruption for Activatable Photodynamic Therapy (pages 1240–1249)

      Cheng S. Jin, Liyang Cui, Fan Wang, Juan Chen and Gang Zheng

      Version of Record online: 27 JAN 2014 | DOI: 10.1002/adhm.201300651

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      Activatable nano-sized beacons for photo­dynamic therapy (PDT): Intact porphysome nanoparticles are inactive for PDT. By incorporating targeting ligands (e.g., folate) into porphysome formulation, receptor-mediated endocytosis facilitates the disruption of the nanostructure inside cells, thus switching back on the photo­dynamic activity of the densely packed porphyrins for effective PDT.

    3. Magnetic Core–Shell Nanocapsules with Dual-Targeting Capabilities and Co-Delivery of Multiple Drugs to Treat Brain Gliomas (pages 1250–1260)

      Jen-Hung Fang, Yen-Ho Lai, Tsung-Lang Chiu, You-Yin Chen, Shang-Hsiu Hu and San-Yuan Chen

      Version of Record online: 13 MAR 2014 | DOI: 10.1002/adhm.201300598

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      Magnetic double emulsion capsules (MDCs) equipped with dual-targeting modalities of lactoferrin and magnetic guidance can achieve the efficacious therapy and reduce the side effect by enhancing the cumulative amount and cell internalization. Once MDCs entrapped in lysosome, doxorubicin, and curcumin can be simultaneously released to overcome multidrug resistance and inhibit the tumor growth of brain glioma through synergistic therapy.

    4. Smart pH-Responsive Nanocarriers Based on Nano-Graphene Oxide for Combined Chemo- and Photothermal Therapy Overcoming Drug Resistance (pages 1261–1271)

      Liangzhu Feng, Kunyang Li, Xiaoze Shi, Min Gao, Jian Liu and Zhuang Liu

      Version of Record online: 20 MAR 2014 | DOI: 10.1002/adhm.201300549

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      A smart pH-responsive drug delivery system is designed using nano-graphene oxide, which is responsive to the tumor microenvironmental pH and shows an excellent ability in overcoming multidrug resistance of cancer cells. A combined chemo- and photothermal therapy is further demonstrated by utilizing the strong near-infrared absorbance of graphene, achieving a synergistic effect in killing drug-resistant cancer cells.

    5. Particle-Stabilized Emulsion Droplets for Gravity-Mediated Targeting in the Posterior Segment of the Eye (pages 1272–1282)

      Yoo C. Kim, Henry F. Edelhauser and Mark R. Prausnitz

      Version of Record online: 20 MAR 2014 | DOI: 10.1002/adhm.201300696

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      Particle-stabilized emulsion droplets with a high-density core can be used to deliver particles as large as 200 nm to specific sites within the posterior segment of the eye based on gravity-mediated targeting.

    6. Using SV119-Gold Nanocage Conjugates to Eradicate Cancer Stem Cells Through a Combination of Photothermal and Chemo Therapies (pages 1283–1291)

      Tianmeng Sun, Yi Wang, Yucai Wang, Jinbin Xu, Xin Zhao, Suwanna Vangveravong, Robert H. Mach and Younan Xia

      Version of Record online: 26 MAR 2014 | DOI: 10.1002/adhm.201400026

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      Cancer stem cells: A new platform is developed to target breast cancer stem cells by functionalizing the surface of Au nanocages with SV119. The interiors of the nanocages could also be loaded with an anticancer drug to achieve a synergetic effect in eradicating cancer stem cells through a combination of photothermal and chemo therapies.

    7. Phosphorylcholine-Coated Semiconducting Polymer Nanoparticles as Rapid and Efficient Labeling Agents for In Vivo Cell Tracking (pages 1292–1298)

      Kanyi Pu, Adam J. Shuhendler, Maija P. Valta, Lina Cui, Matthias Saar, Donna M. Peehl and Jianghong Rao

      Version of Record online: 25 MAR 2014 | DOI: 10.1002/adhm.201300534

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      Phosphorylcholine-coated near-infrared semiconducting polymer nanoparticles are developed to possess rapid cell internalization, high tolerance to reactive oxygen species, and sufficient optical tissue penetration depth. These nanoparticles can be used as universal fluorescent labeling agents for long-term tracking of primary cancer cells in living animals.

    8. Peptide Dendrimer–Doxorubicin Conjugate-Based Nanoparticles as an Enzyme-Responsive Drug Delivery System for Cancer Therapy (pages 1299–1308)

      Chengyuan Zhang, Dayi Pan, Kui Luo, Wenchuan She, Chunhua Guo, Yang Yang and Zhongwei Gu

      Version of Record online: 6 APR 2014 | DOI: 10.1002/adhm.201300601

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      Design, preparation, and characterization of mPEGylated peptide dendrimer–DOX conjugate-based nanoparticles are reported as an enzyme-sensitive drug delivery system for the breast cancer therapy. Both in vitro and in vivo evaluation tumor-bearing mice and healthy mice demonstrate significant increased therapeutic indexes and decreased side effects, indicating the PEGylated peptide dendritic architectures may be used as efficient and safe nanoscale drug delivery vehicles for cancer therapy.

    9. Polymeric-Gold Nanohybrids for Combined Imaging and Cancer Therapy (pages 1309–1325)

      Antonio Topete, Manuel Alatorre-Meda, Eva M. Villar-Alvarez, Susana Carregal-Romero, Silvia Barbosa, Wolfgang J. Parak, Pablo Taboada and Víctor Mosquera

      Version of Record online: 25 APR 2014 | DOI: 10.1002/adhm.201400023

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      Polymeric-gold nanohybrids (PGNH NPs) co-loaded with doxorubicin and SPIONs, and functionalized with folic acid are tested for multimodal therapy (photothermal- and chemo-therapy) and simultaneous magnetic resonance and optical imaging. Light-triggered drug release is demonstrated as well as an enhanced cellular uptake by effect of folic acid and external magnetic field. PGNH NPs are highly selective and show synergistic cytotoxic effect.

    10. A Symmetrical Fluorous Dendron-Cyanine Dye-Conjugated Bimodal Nanoprobe for Quantitative 19F MRI and NIR Fluorescence Bioimaging (pages 1326–1333)

      Zhe Wang, Xuyi Yue, Yu Wang, Chunqi Qian, Peng Huang, Marty Lizak, Gang Niu, Fu Wang, Pengfei Rong, Dale O. Kiesewetter, Ying Ma and Xiaoyuan Chen

      Version of Record online: 2 MAY 2014 | DOI: 10.1002/adhm.201400088

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      19F MRI and optical imaging are two powerful noninvasive molecular imaging modalities in biomedical applications. A bimodal nanoprobe incorporating a symmetrical fluorous dendron-cyanine dye single molecule is developed by addressing shortcomings of conventional contrast agents to explore the quantitative 19F MRI and fluorescent imaging. This nanoprobe can hold great potential for quantitative and sensitive multi-modal bioimaging.

    11. Graphene-Based Electroresponsive Scaffolds as Polymeric Implants for On-Demand Drug Delivery (pages 1334–1343)

      Ania Servant, Veronica Leon, Dhifaf Jasim, Laura Methven, Patricia Limousin, Ester Vazquez Fernandez-Pacheco, Maurizio Prato and Kostas Kostarelos

      Version of Record online: 5 MAY 2014 | DOI: 10.1002/adhm.201400016

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      The fabrication of graphene hydrogel hybrid electroactive scaffolds for on-demand drug delivery is shown. In this study, an illustration of how the heat dissipating properties of graphene can provide significant advantages in the design of electroresponsive hydrogels, able to maintain optimal functionality by overcoming adverse effects due to unwanted heating, is offered.

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