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Drug Delivery

The importance of drug delivery to chemists, medicinal and otherwise, has increased since the advent of integrated drug discovery processes. Physicochemical and biological barriers, pathways for drug delivery, formulation, pharmacokinetic and pharmacodynamic issues, metabolism, and cell culture models used in studying drug delivery are just some of the topics that make drug delivery an exciting field for researchers.

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Seung Beom Kim, Tae Heon Lee, Il Yoon, Young Key Shim, Woo Kyoung Lee
Gold Nanorod–Photosensitizer Complex Obtained by Layer-by-Layer Method for Photodynamic/Photothermal Therapy In Vitro [Communication]

Gold Nanorod–Photosensitizer Complex Obtained by Layer-by-Layer Method for Photodynamic/Photothermal Therapy In Vitro

Double up: A gold nanorod (GNR)–photosensitizer (PS) complex, which was prepared by using the LbL method, exhibits high anticancer activity in vitro using a synergistic therapy of photothermal therapy (PTT) followed by photodynamic therapy (PDT). In this system, PTT controls the PS release to maximize 1O2 photogeneration for PDT.

Chem. Asian J., January 28, 2015, DOI: 10.1002/asia.201403193

Weishuo Li, Liwen Huang, Xiaoying Ying, You Jian, Yuan Hong, Fuqiang Hu, Yongzhong Du
Antitumor Drug Delivery Modulated by A Polymeric Micelle Having Upper Critical Solution Temperature [Communication]

Antitumor Drug Delivery Modulated by A Polymeric Micelle Having Upper Critical Solution Temperature

Smart device: Poly(AAm-co-AN)-g-PEG micelles were used as a temperature-triggered drug delivery system based on their upper critical solution temperature. The polymeric micelles displayed a good drug release profile both in vitro and in vivo. Additionally, an excellent antitumor efficiency was achieved. DOX=doxorubicin.

Angew. Chem. Int. Ed., January 28, 2015, DOI: 10.1002/anie.201411524

Giulia Tuci, Lapo Luconi, Andrea Rossin, Francesco Baldini, Stefano Cicchi, Sara Tombelli, Cosimo Trono, Ambra Giannetti, Ilse Manet, Stefano Fedeli, Alberto Brandi, Giuliano Giambastiani
A Hetero-Bifunctional Spacer for the Smart Engineering of Carbon-Based Nanostructures [Full Paper]

A Hetero-Bifunctional Spacer for the Smart Engineering of Carbon-Based Nanostructures

Building on solid foundations: A hetero-bifunctional linker joining a “cleavable” disulfide moiety and a “clickable” terminal acetylene group was synthesized and used to decorate carbon nanotubes (CNTs). When used in combination with other selected terminal acetylene molecules, the linker can impart multimodality through a controlled click reaction to give carbon nanohybrids (see figure).

ChemPlusChem, January 21, 2015, DOI: 10.1002/cplu.201402391

Juan Yan, Chongya Hu, Ping Wang, Bin Zhao, Xiangyuan Ouyang, Juan Zhou, Rui Liu, Dannong He, Chunhai Fan, Shiping Song
Growth and Origami Folding of DNA on Nanoparticles for High-Efficiency Molecular Transport in Cellular Imaging and Drug Delivery [Communication]

Growth and Origami Folding of DNA on Nanoparticles for High-Efficiency Molecular Transport in Cellular Imaging and Drug Delivery

A novel 3D gold-DNA superstructure based on DNA growing and origami folding on gold nanoparticles had been fabricated. The new 3D superstructures exhibit great potential for high-efficiency molecule transport for use in cellular imaging and drug delivery.

Angew. Chem. Int. Ed., January 19, 2015, DOI: 10.1002/anie.201408247

Korbinian Brunner, Johannes Harder, Tobias Halbach, Julian Willibald, Fabio Spada, Felix Gnerlich, Konstantin Sparrer, Andreas Beil, Leonhard Möckl, Christoph Bräuchle, Karl-Klaus Conzelmann, Thomas Carell
Cell-Penetrating and Neurotargeting Dendritic siRNA Nanostructures [Communication]

Cell-Penetrating and Neurotargeting Dendritic siRNA Nanostructures

siRNA dendrimers with an anandamide receptor ligand are accessible through a click-chemistry approach, and are taken up even by sensitive neural cells. Silencing of two key proteins of the rabies virus was achieved, allowing the suppression of the viral titer in infected neurons below the detection limit.

Angew. Chem. Int. Ed., December 17, 2014, DOI: 10.1002/anie.201409803

Silvia Cauteruccio, Cristina Bartoli, Claudio Carrara, Davide Dova, Cesare Errico, Giulia Ciampi, Dinuccio Dinucci, Emanuela Licandro, Federica Chiellini
A Nanostructured PLGA System for Cell Delivery of a Tetrathiahelicene as a Model for Helical DNA Intercalators [Communication]

A Nanostructured PLGA System for Cell Delivery of a Tetrathiahelicene as a Model for Helical DNA Intercalators

Deliver the goods: A preliminary study of the cellular uptake of a nanoconstruct obtained by loading poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a tetrathiahelicene conjugated to a fluorescent rhodamine probe has been carried out. The ability to internalize the tetrathiahelicene and deliver it intracellularly has been investigated by means of cytotoxicity and cell uptake tests on Balb/3T3 clone A31 fibroblasts (see figure).

ChemPlusChem, December 4, 2014, DOI: 10.1002/cplu.201402347

Valentina Giglio, Valentina Oliveri, Maurizio Viale, Rosaria Gangemi, Giovanni Natile, Francesco P. Intini, Graziella Vecchio
Folate–Cyclodextrin Conjugates as Carriers of the Platinum(IV) Complex LA-12 [Full Paper]

Folate–Cyclodextrin Conjugates as Carriers of the Platinum(IV) Complex LA-12

Drugs included: The antitumor drug cistranscis-[PtCl2(CH3CO2)2(adamantlyamine)(NH3)] (LA-12) co-administered with 3- or 6-functionalised β-cyclodextrin conjugated with γ-folate (βCyD3-FAγ or βCyD6-FAγ) as an inclusion complex showed IC50 values significantly lower than that of LA-12 alone or LA-12 co-administered with βCyD in folate receptor-overexpressing cancer cells (see figure).

ChemPlusChem, November 11, 2014, DOI: 10.1002/cplu.201402342

Wenqian Wang, Linfeng Chen, Li-ping Xu, Hongwu Du, Yongqiang Wen, Yanlin Song, Xueji Zhang
A Free-Blockage Controlled Release System Based on the Hydrophobic/Hydrophilic Conversion of Mesoporous Silica Nanopores [Full Paper]

A Free-Blockage Controlled Release System Based on the Hydrophobic/Hydrophilic Conversion of Mesoporous Silica Nanopores

An open and shut case: A pH-responsive free-blockage release system was achieved through controlling the hydrophobic/hydrophilic conversion of mesoporous silica nanopores (see figure). This system could have the ability of continuous infection to tumor cells with high drug-delivery efficiency and few side effects.

Chem. Eur. J. 2015, 21, No. 06, 2680-2685

Ying-Jie Zhu, Feng Chen
pH-Responsive Drug-Delivery Systems [Focus Review]

pH-Responsive Drug-Delivery Systems

Get a response! pH-Responsive drug-delivery systems have promising applications because they are “smart” or “intelligent” in overcoming the shortcomings of conventional drug formulations and are able to deliver drugs in a controlled manner at specific sites and times, which results in high therapeutic efficacy. Recent progress obtained for pH-responsive drug-delivery systems and future perspectives is presented.

Chem. Asian J. 2015, 10, No. 02, 284-305

Nelli Rahanyan-Kägi, Simone Aleandri, Chiara Speziale, Raffaele Mezzenga, Ehud M. Landau
Stimuli-Responsive Lipidic Cubic Phase: Triggered Release and Sequestration of Guest Molecules [Communication]

Stimuli-Responsive Lipidic Cubic Phase: Triggered Release and Sequestration of Guest Molecules

Delivery on demand: New stimuli-responsive lipidic cubic phases (LCPs) made up of designer host–guest systems are presented (see scheme). These biocompatible nanomaterials exhibit efficient pH- and light-induced binding, release and sequestration of hydrophilic dyes, while preserving a cubic symmetry, as was evidenced by small-angle X-ray scattering.

Chem. Eur. J. 2015, 21, No. 05, 1873-1877

Wookhyun Kim, Carolyn Haller, Erbin Dai, Xiowei Wang, Christoph E. Hagemeyer, David R. Liu, Karlheinz Peter, Elliot L. Chaikof
Targeted Antithrombotic Protein Micelles [Communication]

Targeted Antithrombotic Protein Micelles

Site-specific: An activated platelet-specific antibody and antithrombotic protein were site-specifically conjugated to the corona of protein nanomicelles for efficient detection and inhibition of thrombus formation. These multifunctional protein micelles provide a promising approach to the site-specific delivery of a potent antithrombotic agent, thus reducing the dose and bleeding risk. aPC=activated protein C, Th=thrombin.

Angew. Chem. Int. Ed. 2015, 54, No. 05, 1461-1465

Dual Photo- and pH-Responsive Supramolecular Nanocarriers Based on Water-Soluble Pillar[6]arene and Different Azobenzene Derivatives for Intracellular Anticancer Drug Delivery

On the double: Two types of nanocarriers are fabricated: supramolecular micelles formed from water-soluble pillar[6]arene (WP6) and azobenzene derivative G1, which gradually transform into layered structures, and supramolecular vesicles formed by WP6 and guest G2, which exhibit dual photo- and pH-responsive behavior (see figure). Mitoxantrone (MTZ)-loaded vesicles show a similar therapeutic effect for cancer cells to free MTZ and reduced damage to normal cells.

Chem. Eur. J. 2015, 21, No. 03, 1208-1220

Yang Zhao, Zhong Luo, Menghuan Li, Qiuyu Qu, Xing Ma, Shu-Hong Yu, Yanli Zhao
A Preloaded Amorphous Calcium Carbonate/Doxorubicin@Silica Nanoreactor for pH-Responsive Delivery of an Anticancer Drug [Communication]

A Preloaded Amorphous Calcium Carbonate/Doxorubicin@Silica Nanoreactor for pH-Responsive Delivery of an Anticancer Drug

Precise release of doxorubicin (DOX) in the weakly acidic microenvironment of cancer cells has been achieved with an amorphous calcium carbonate/doxorubicin@silica (ACC–DOX@silica) nanoreactor. Only low drug leakage occurs in physiological and lysosomal/endosomal environments, but at pH 6.5 the drug is specifically released and results in efficient cell death.

Angew. Chem. Int. Ed. 2015, 54, No. 03, 919-922

ZnO-Functionalized Upconverting Nanotheranostic Agent: Multi-Modality Imaging-Guided Chemotherapy with On-Demand Drug Release Triggered by pH

A nanotheranostic agent: A ZnO-functionalized upconverting nanotheranostic platform for multi-modality bioimaging (UCL/CT/MRI) and pH-triggered on-demand drug release has been successfully fabricated (see picture). Nontoxic ZnO can play the role of a “gatekeeper” to block the drug in the mesopores of the as-prepared agents until ZnO is dissolved in the acidic environment around tumors.

Angew. Chem. Int. Ed. 2015, 54, No. 02, 536-540

Cuisong Zhou, Tao Chen, Cuichen Wu, Guizhi Zhu, Liping Qiu, Cheng Cui, Weijia Hou, Weihong Tan
Aptamer CaCO3 Nanostructures: A Facile, pH-Responsive, Specific Platform for Targeted Anticancer Theranostics [Full Paper]

Aptamer CaCO3 Nanostructures: A Facile, pH-Responsive, Specific Platform for Targeted Anticancer Theranostics

Hitting the mark: An anticancer theranostic platform with a high drug-loading capacity, termed an aptamer-functionalized calcium carbonate (CaCO3) nanostructure (apt-CCN), is reported (see picture). This smart nanostructure selectively reaches the lysosomes through receptor-mediated endocytosis and is responsive to the relatively low lysosome pH (4.5–5.5), which facilitates the release of doxorubicin.

Chem. Asian J. 2015, 10, No. 01, 166-171

Targeted Treatment of Cancer with Nanotherapeutics Based on Mesoporous Silica Nanoparticles

Nanotherapeutics are designed and constructed from mesoporous silica nanoparticles for the targeted treatment of cancer based on characteristics of tumor tissues. The picture shows drug delivery triggered by the acidic extracellular environment of cancer, endocytosis of the drug carrier, and intracellular release of cargo drugs.

ChemPlusChem 2015, 80, No. 01, 26-36

Huijie Zhu, Jin Li, Xiao-Bing Zhang, Mao Ye, Weihong Tan
Nucleic Acid Aptamer-Mediated Drug Delivery for Targeted Cancer Therapy [Minireview]

Nucleic Acid Aptamer-Mediated Drug Delivery for Targeted Cancer Therapy

Targeted & Specific: The applications of nucleic acid aptamers in cancer are reviewed. Single-stranded (ss) oligonucleotide (DNA or RNA)-based aptamers conjugated with drugs and nanomaterials are covered in detail, highlighting their therapeutic potential while acknowledging the challenges that remain to be overcome.

ChemMedChem 2015, 10, No. 01, 39-45

Stimuli-Responsive Polymeric Nanoparticles for Nanomedicine

Bringing life from cell death: Stimuli-responsive polymeric nanoparticles can respond to the microenvironment of a particular disease and its cells. Internal triggers as well as external devices permit temporally and spatially controlled drug delivery. The development of well-defined nanomedicines is critical for their behavior in vivo.

ChemMedChem 2015, 10, No. 01, 24-38

Tianmeng Sun, Yu Shrike Zhang, Bo Pang, Dong Choon Hyun, Miaoxin Yang, Younan Xia
Engineered Nanoparticles for Drug Delivery in Cancer Therapy [Review]

Engineered Nanoparticles for Drug Delivery in Cancer Therapy

On the way to nanomedicine: Considerable advances in the development of nanoparticles for cancer therapy have been made in recent years. Nanoparticle-based drug-delivery systems offer advantages with regard to multidrug resistance, systemic delivery, and clearance, and enable for example specific tumor targeting and controlled release of therapeutic agents.

Angew. Chem. Int. Ed. 2014, 53, No. 46, 12320-12364

Pedro M. S. D. Cal, Gonçalo J. L. Bernardes, Pedro M. P. Gois
Cysteine-Selective Reactions for Antibody Conjugation [Highlight]

Cysteine-Selective Reactions for Antibody Conjugation

Moving tracks from maleimide: New site-selective protein modification reactions at cysteine have been developed. Unlike conventional maleimide conjugation, which results in a labile thioether succinimide, the new bioconjugation reactions result in stable conjugates and provide opportunities to develop a new generation of homogeneous, stable, and therapeutically useful conjugates.

Angew. Chem. Int. Ed. 2014, 53, No. 40, 10585-10587

Sandra García-Gallego, Gonçalo J. L. Bernardes
Carbon-Monoxide-Releasing Molecules for the Delivery of Therapeutic CO In Vivo [Minireview]

Carbon-Monoxide-Releasing Molecules for the Delivery of Therapeutic CO In Vivo

On target: Carbon-monoxide-releasing molecules (CORMs) are promising agents for the treatment of several diseases. CORMs are particularly good for enabling CO delivery in a controlled manner without affecting oxygen transport by hemoglobin. Significant progress in the methods for CO detection in live cells and the understanding of the reactivity of CORMs in vivo provides insights into CO biology and the design of safer, and more selective and efficient CORMs for clinical use.

Angew. Chem. Int. Ed. 2014, 53, No. 37, 9712-9721

Sven Kruspe, Florian Mittelberger, Kristina Szameit, Ulrich Hahn
Aptamers as Drug Delivery Vehicles [Review]

Aptamers as Drug Delivery Vehicles

Selective delivery: Active drug targeting enhances the efficacy and specificity of systemic therapeutics. Aptamers, artificial nucleic acid ligands, represent powerful targeting tools that can act as cell-specific drug carriers. The advancements from the past decade have provided various approaches that open new gateways for drug administration in cancer therapy.

ChemMedChem 2014, 9, No. 09, 1998-2011

Dong Choon Hyun, Nathanael S. Levinson, Unyong Jeong, Younan Xia
Emerging Applications of Phase-Change Materials (PCMs): Teaching an Old Dog New Tricks [Review]

Emerging Applications of Phase-Change Materials (PCMs): Teaching an Old Dog New Tricks

PCMs on the rise: As a result of their sharp melting points and large heats of fusion during phase transition, phase-change materials (PCMs) have already found commercial use in thermal management. The vast potential of this class of fascinating materials has recently been tapped in a diverse array of high-tech applications such as controlled release, information storage, sensing/detection, and barcoding.

Angew. Chem. Int. Ed. 2014, 53, No. 15, 3780-3795

Sabrina Nowag, Rainer Haag
pH-Responsive Micro- and Nanocarrier Systems [Highlight]

pH-Responsive Micro- and Nanocarrier Systems

Release on demand: The pH gradients between extra- and intracellular regions can be utilized for the controlled release of drugs and biological cargos from delivery systems. Biocompatible carrier systems with pH-cleavable units must fulfill many other criteria as well, for example, a long blood circulation time. This can be achieved by tailored micro- and nanocarriers based on macromolecular architectures or stable self-assembled systems.

Angew. Chem. Int. Ed. 2014, 53, No. 01, 49-51

Wei Cao, Yuwei Gu, Myriam Meineck, Huaping Xu
The Combination of Chemotherapy and Radiotherapy towards More Efficient Drug Delivery [Focus Review]

The Combination of Chemotherapy and Radiotherapy towards More Efficient Drug Delivery

Missing a piece? We propose the idea of combining regular chemotherapy with radiation therapy to minimize side effects and to increase drug-delivery efficiency. The unfinished puzzle in the picture shows the Aesculapian snake—the symbol of pharmacy and cure—to remind us that there is still a gap between potent chemotherapeutics and radiotherapy. We hope the emerging research area summarized in this Focus Review can function as the connecting pieces to solve the puzzle of an effective and comprehensive treatment.

Chem. Asian J. 2014, 9, No. 01, 48-57

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