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Special Issue "Dendrimers in Medicine and Biotechnology"

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (15 July 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Zofia Urbanczyk-Lipkowska (Website)

Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka Str. 44/52, 01-224 Warsaw, Poland
Interests: dendrimer chemistry; solid phase structural studies of branched molecules; photochromic compounds; chiral coordination polymers

Special Issue Information

Dear Colleagues,

During last 20 years of dendrimers history – these eye-catching polymeric molecules generated non-precedented interest in many areas, including biomedical and pharmaceutical research. Only this year over 70 review articles on dendrimers synthesis, structure and various properties and applications have been published. Due to polyvalency, capability to control chemistry and properties of the surface area and molecular interior, dendrimers exhibit valuable properties of nanoscale delivery systems, bioconjugates for in-vitro immunoassays for antigens, and materials for vaccination. Their potential in treatment of lifestyle and civilization diseases such as cancer, diabetes, viral and microbial infections, Alzheimer and prion-associated diseases, etc. has also been recognized. Bioactivity of the designed dendrimers suggests them as promising therapeutic agents in contemporary regenerative medicine, involved in wound healing, tissue and cartilage reconstruction as well as bone mineralization. The potential applications of de novo – designed dendrimers in such areas as boron neutron capture therapy, as MRI contrast reagents, and materials for enhanced transfection cannot be overlooked. First applications of dendrimers for topical treatments against herpes simplex virus or for prevention of HIV transmission will be available soon.

This special issue of Molecules “Dendrimers in Medicine and Biotechnology” welcomes previously unpublished manuscripts covering aspects of new synthetic and characterization methods of dendrimers, new molecular entities, their therapeutic potential in the area of medicine and biotechnology.

Prof. Zofia Urbanczyk-Lipkowska
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).

Keywords

  • dendrimers
  • synthesis
  • haracterization
  • biomedical
  • regenerative medicine
  • biotechnology

Published Papers (14 papers)

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Research

Jump to: Review

Open AccessArticle Investigation of Dendriplexes by Ion Mobility-Mass Spectrometry
Molecules 2014, 19(12), 20731-20750; doi:10.3390/molecules191220731
Received: 24 July 2014 / Revised: 22 October 2014 / Accepted: 27 October 2014 / Published: 12 December 2014
Cited by 1 | PDF Full-text (3141 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Highly branched polyamidoamine (PAMAM) dendrimers presenting biological activities have been envisaged as non-viral gene delivery vectors. They are known to associate with nucleic acid (DNA) in non-covalent complexes via electrostatic interactions. Although their transfection efficiency has been proved, PAMAMs present a significant [...] Read more.
Highly branched polyamidoamine (PAMAM) dendrimers presenting biological activities have been envisaged as non-viral gene delivery vectors. They are known to associate with nucleic acid (DNA) in non-covalent complexes via electrostatic interactions. Although their transfection efficiency has been proved, PAMAMs present a significant cytotoxicity due to their cationic surface. To overcome such a drawback, different chemical modifications of the PAMAM surface have been reported such as the attachment of hydrophobic residues. In the present work, we studied the complexation of DNA duplexes with different low-generation PAMAM; ammonia-cored G0(N) and G1(N) PAMAM, native or chemically modified with aromatic residues, i.e., phenyl-modified-PAMAM G0(N) and phenylalanine-modified-PAMAM G1(N). To investigate the interactions involved in the PAMAM/DNA complexes, also called dendriplexes, we used electrospray ionization (ESI) coupled to ion mobility spectrometry-mass-spectrometry (IM-MS). ESI is known to allow the study of non-covalent complexes in native conditions while IM-MS is a bidimensional separation technique particularly useful for the characterization of complex mixtures. IM-MS allows the separation of the expected complexes, possible additional non-specific complexes and the free ligands. Tandem mass spectrometry (MS/MS) was also used for the structural characterization. This work highlights the contribution of IM-MS and MS/MS for the study of small dendriplexes. The stoichiometries of the complexes and the equilibrium dissociation constants were determined. The [DNA/native PAMAM] and [DNA/modified-PAMAM] dendriplexes were compared. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Open AccessArticle Optimized Solid Phase-Assisted Synthesis of Dendrons Applicable as Scaffolds for Radiolabeled Bioactive Multivalent Compounds Intended for Molecular Imaging
Molecules 2014, 19(6), 6952-6974; doi:10.3390/molecules19066952
Received: 22 April 2014 / Revised: 22 May 2014 / Accepted: 23 May 2014 / Published: 27 May 2014
Cited by 2 | PDF Full-text (998 KB) | HTML Full-text | XML Full-text
Abstract
Dendritic structures, being highly homogeneous and symmetric, represent ideal scaffolds for the multimerization of bioactive molecules and thus enable the synthesis of compounds of high valency which are e.g., applicable in radiolabeled form as multivalent radiotracers for in vivo imaging. As the [...] Read more.
Dendritic structures, being highly homogeneous and symmetric, represent ideal scaffolds for the multimerization of bioactive molecules and thus enable the synthesis of compounds of high valency which are e.g., applicable in radiolabeled form as multivalent radiotracers for in vivo imaging. As the commonly applied solution phase synthesis of dendritic scaffolds is cumbersome and time-consuming, a synthesis strategy was developed that allows for the efficient assembly of acid amide bond-based highly modular dendrons on solid support via standard Fmoc solid phase peptide synthesis protocols. The obtained dendritic structures comprised up to 16 maleimide functionalities and were derivatized on solid support with the chelating agent DOTA. The functionalized dendrons furthermore could be efficiently reacted with structurally variable model thiol-bearing bioactive molecules via click chemistry and finally radiolabeled with 68Ga. Thus, this solid phase-assisted dendron synthesis approach enables the fast and straightforward assembly of bioactive multivalent constructs for example applicable as radiotracers for in vivo imaging with Positron Emission Tomography (PET). Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Open AccessArticle Intracellular Environment-Responsive Stabilization of Polymer Vesicles Formed from Head-Tail Type Polycations Composed of a Polyamidoamine Dendron and Poly(L-lysine)
Molecules 2013, 18(10), 12168-12179; doi:10.3390/molecules181012168
Received: 6 August 2013 / Revised: 18 September 2013 / Accepted: 23 September 2013 / Published: 30 September 2013
Cited by 3 | PDF Full-text (1165 KB) | HTML Full-text | XML Full-text
Abstract
For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and [...] Read more.
For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and a poly(L-lysine) tail (PAMAM dendron-PLL), through the introduction of disulfide bonds between the PLL tails. Disulfide bonds were successfully introduced through the reaction of Lys residues in the PAMAM dendron-PLL polymer vesicles with 2-iminothiolane. The stabilization of PAMAM dendron-PLL polymer vesicles was confirmed by dynamic light scattering measurements. In acid-base titration experiments, nanocapsules cross-linked by disulfide bonds had a buffering effect during the cellular uptake process. The PAMAM dendron-PLL nanocapsules were used to incorporate the fluorescent dyes rhodamine 6G and fluorescein as a drug model. Cationic rhodamine 6G was generally not released from the nanocapsules because of the electrostatic barrier of the PLL membrane. However, the nanocapsules were destabilized at high glutathione concentrations corresponding to intracellular concentrations. Rhodamine 6G was immediately released from the nanocapsules because of destabilization upon the cleavage of disulfide bonds. This release of rhodamine 6G from the nanocapsules was also observed in HeLa cells by laser confocal microscopy. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Open AccessArticle Analysis of Biotinylated Generation 4 Poly(amidoamine) (PAMAM) Dendrimer Distribution in the Rat Brain and Toxicity in a Cellular Model of the Blood-Brain Barrier
Molecules 2013, 18(9), 11537-11552; doi:10.3390/molecules180911537
Received: 23 July 2013 / Revised: 3 September 2013 / Accepted: 10 September 2013 / Published: 17 September 2013
Cited by 6 | PDF Full-text (3257 KB) | HTML Full-text | XML Full-text
Abstract
Dendrimers are highly customizable nanopolymers with qualities that make them ideal for drug delivery. The high binding affinity of biotin/avidin provides a useful approach to fluorescently label synthesized dendrimer-conjugates in cells and tissues. In addition, biotin may facilitate delivery of dendrimers through [...] Read more.
Dendrimers are highly customizable nanopolymers with qualities that make them ideal for drug delivery. The high binding affinity of biotin/avidin provides a useful approach to fluorescently label synthesized dendrimer-conjugates in cells and tissues. In addition, biotin may facilitate delivery of dendrimers through the blood-brain barrier (BBB) via carrier-mediated endocytosis. The purpose of this research was to: (1) measure toxicity using lactate dehydrogenase (LDH) assays of generation (G)4 biotinylated and non-biotinylated poly(amidoamine) (PAMAM) dendrimers in a co-culture model of the BBB, (2) determine distribution of dendrimers in the rat brain, kidney, and liver following systemic administration of dendrimers, and (3) conduct atomic force microscopy (AFM) on rat brain sections following systemic administration of dendrimers. LDH measurements showed that biotinylated dendrimers were toxic to cell co-culture after 48 h of treatment. Distribution studies showed evidence of biotinylated and non-biotinylated PAMAM dendrimers in brain. AFM studies showed evidence of dendrimers only in brain tissue of treated rats. These results indicate that biotinylation does not decrease toxicity associated with PAMAM dendrimers and that biotinylated PAMAM dendrimers distribute in the brain. Furthermore, this article provides evidence of nanoparticles in brain tissue following systemic administration of nanoparticles supported by both fluorescence microscopy and AFM. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Open AccessArticle DNA Condensation by Partially Acetylated Poly(amido amine) Dendrimers: Effects of Dendrimer Charge Density on Complex Formation
Molecules 2013, 18(9), 10707-10720; doi:10.3390/molecules180910707
Received: 1 August 2013 / Revised: 29 August 2013 / Accepted: 30 August 2013 / Published: 3 September 2013
Cited by 8 | PDF Full-text (1153 KB) | HTML Full-text | XML Full-text
Abstract
The ability of poly(amido amine) (or PAMAM) dendrimers to condense semiflexible dsDNA and penetrate cell membranes gives them great potential in gene therapy and drug delivery but their high positive surface charge makes them cytotoxic. Here, we describe the effects of partial [...] Read more.
The ability of poly(amido amine) (or PAMAM) dendrimers to condense semiflexible dsDNA and penetrate cell membranes gives them great potential in gene therapy and drug delivery but their high positive surface charge makes them cytotoxic. Here, we describe the effects of partial neutralization by acetylation on DNA condensation using light scattering, circular dichroism, and single molecule imaging of dendrimer-DNA complexes combed onto surfaces and tethered to those surfaces under flow. We find that DNA can be condensed by generation-five (G5) dendrimers even when the surface charges are more than 65% neutralized, but that such dendrimers bind negligibly when an end-tethered DNA is stretched in flow. We also find that when fully charged dendrimers are introduced by flow to end-tethered DNA, all DNA molecules become equally highly coated with dendrimers at a rate that becomes very fast at high dendrimer concentration, and that dendrimers remain bound during subsequent flow of dendrimer-free buffer. These results suggest that the presence of dendrimer-free DNA coexisting with dendrimer-bound DNA after bulk mixing of the two in solution may result from diffusion-limited irreversible dendrimer-DNA binding, rather than, or in addition to, the previously proposed cooperative binding mechanism of dendrimers to DNA. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Open AccessArticle An Azabisphosphonate-Capped Poly(phosphorhydrazone) Dendrimer for the Treatment of Endotoxin-Induced Uveitis
Molecules 2013, 18(8), 9305-9316; doi:10.3390/molecules18089305
Received: 15 July 2013 / Revised: 26 July 2013 / Accepted: 1 August 2013 / Published: 5 August 2013
Cited by 9 | PDF Full-text (871 KB) | HTML Full-text | XML Full-text
Abstract
Over the last decade, different types of dendrimers have shown anti-inflammatory properties in their own right. In particular, we have shown that poly(phosphorhydrazone) (PPH) dendrimers are able to foster an efficient anti-inflammatory response in human monocytes and can resolve the main physiopathological [...] Read more.
Over the last decade, different types of dendrimers have shown anti-inflammatory properties in their own right. In particular, we have shown that poly(phosphorhydrazone) (PPH) dendrimers are able to foster an efficient anti-inflammatory response in human monocytes and can resolve the main physiopathological features of chronic arthritis in mice at 1 mg/kg. Here we afford new insights into the therapeutic potential of an azabisphosphonate-capped dendrimer (dendrimer ABP). We have challenged its anti-inflammatory and immuno-modulatory properties in a robust rat model of acute uveitis induced by lipopolysaccharide (LPS). We show that dendrimer ABP at 2 µg/eye is as efficient as the “gold standard” dexamethasone at 20 µg/eye. We have demonstrated that the effect of dendrimer ABP is mediated at least through an increase of the production of the anti-inflammatory Interleukin(IL)-10 cytokine. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Open AccessArticle The Effect of PAMAM Dendrimers on the Antibacterial Activity of Antibiotics with Different Water Solubility
Molecules 2013, 18(7), 8607-8617; doi:10.3390/molecules18078607
Received: 20 June 2013 / Revised: 12 July 2013 / Accepted: 16 July 2013 / Published: 22 July 2013
Cited by 10 | PDF Full-text (226 KB) | HTML Full-text | XML Full-text
Abstract
Erythromycin (EM) and tobramycin (TOB) are well-known and widely used antibiotics, belonging to different therapeutic groups: macrolide and aminoglycoside, respectively. Moreover, they possess different solubility: EM is slightly soluble and TOB is freely soluble in water. It was previously demonstrated that PAMAM [...] Read more.
Erythromycin (EM) and tobramycin (TOB) are well-known and widely used antibiotics, belonging to different therapeutic groups: macrolide and aminoglycoside, respectively. Moreover, they possess different solubility: EM is slightly soluble and TOB is freely soluble in water. It was previously demonstrated that PAMAM dendrimers enhanced the pharmacological activity of antifungal drugs by increasing their solubility. Therefore, it appears interesting to investigate the effect of PAMAM-NH2 and PAMAM-OH dendrimers generation 2 (G2) and generation 3 (G3) on the antibacterial activity of antibiotics with different water solubility. In this study it was shown that the aqueous solubility of EM was significantly increased by PAMAM dendrimers (PAMAM-NH2 and PAMAM-OH caused about 8- and 7- fold solubility increases, respectively). However, it was indicated that despite the increase in the solubility, there was only slight influence on the antibacterial activity of EM (2- and 4- fold decreases in the MBC values of EM in the presence of PAMAM-OH G3 and PAMAM-NH2 G2 or G3 for strains of Staphylococcus aureus were noted, respectively). It was also found that there was no influence of PAMAM on the antibacterial activity of hydrophilic TOB. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Open AccessArticle Novel Antimicrobial Peptide Dendrimers with Amphiphilic Surface and Their Interactions with Phospholipids — Insights from Mass Spectrometry
Molecules 2013, 18(6), 7120-7144; doi:10.3390/molecules18067120
Received: 9 April 2013 / Revised: 4 June 2013 / Accepted: 6 June 2013 / Published: 18 June 2013
Cited by 7 | PDF Full-text (977 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of new peptide dendrimers with amphiphilic surface, designed around a dendronized ornithine (Orn) core were synthesized and characterized by ESI-MS, 1H-, 13C- NMR, and CD spectrometry. An improved antimicrobial potency against S. aureus and E. coli was detected [...] Read more.
A series of new peptide dendrimers with amphiphilic surface, designed around a dendronized ornithine (Orn) core were synthesized and characterized by ESI-MS, 1H-, 13C- NMR, and CD spectrometry. An improved antimicrobial potency against S. aureus and E. coli was detected as a result of an increased charge, higher branching and variable lipophilicity of the residues located at the C-terminus. Minimal inhibitory concentration (MIC) values indicated that the selected dendrimers were not sensitive to the physiological concentration of Na+ and K+ ions (100 mM), but expressed reduced potency at 10 mM concentration of Mg2+ and Ca2+ ions. Circular dichroism (CD) curves measured under various conditions revealed structure and solvent-dependent curve evolution. ESI-MS studies of gas-phase interactions between selected dendrimers and both anionic (DMPG) and neutral (DMPC) phospholipids revealed the presence of variously charged dendrimer/phospholipid aggregates with 1:1 to 1:5 stoichiometry. The collision-induced fragmentation (CID) of the most abundant [dendrimer/phospholipid]2+ ions of the 1:1 stoichiometry demonstrated that the studied dendrimers formed stronger complexes with anionic DMPG. Both phospholipids have higher affinity towards dendrimers with a more compact structure. Higher differences in CID energy necessary for dissociation of 50% of the complex formed by dendrimers with DMPG vs. DMPC (DCID50) correlate with a lower hemotoxicity. Mass spectrometry results suggest that for a particular group of compounds the DCID50 might be one of the important factors explaining selectivity of antimicrobial peptides and their branched analogs targeting the bacterial membrane. Both circular dichroism and mass spectrometry studies demonstrated that dendrimers of Nα- and Nε-series possess a different conformation in solution and different affinity to model phospholipids, what might influence their specific microbicidal mechanism. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Open AccessArticle Vortex-Induced Alignment of a Water Soluble Supramolecular Nanofiber Composed of an Amphiphilic Dendrimer
Molecules 2013, 18(6), 7071-7080; doi:10.3390/molecules18067071
Received: 14 May 2013 / Revised: 7 June 2013 / Accepted: 8 June 2013 / Published: 17 June 2013
Cited by 2 | PDF Full-text (511 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We have synthesized a novel amphiphilic naphthalene imide bearing a cationic dendrimer wedge (NID). NID molecules in water self-assemble to form a two-dimensional ribbon, which further coils to give a linear supramolecular nanofiber. The sample solution showed linear dichroism (LD) upon stirring [...] Read more.
We have synthesized a novel amphiphilic naphthalene imide bearing a cationic dendrimer wedge (NID). NID molecules in water self-assemble to form a two-dimensional ribbon, which further coils to give a linear supramolecular nanofiber. The sample solution showed linear dichroism (LD) upon stirring of the solution, where NID nanofibers dominantly align at the center of vortex by hydrodynamic interaction with the downward torsional flows. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Open AccessArticle Phosphorus Dendrimers as Carriers of siRNA—Characterisation of Dendriplexes
Molecules 2013, 18(4), 4451-4466; doi:10.3390/molecules18044451
Received: 18 March 2013 / Revised: 3 April 2013 / Accepted: 11 April 2013 / Published: 15 April 2013
Cited by 7 | PDF Full-text (545 KB) | HTML Full-text | XML Full-text
Abstract
There are many types of dendrimers used as nanomolecules for gene delivery but there is still an ongoing search for ones that are able to effectively deliver drugs to cells. The possibility of gene silencing using siRNA gives hope for effective treatment [...] Read more.
There are many types of dendrimers used as nanomolecules for gene delivery but there is still an ongoing search for ones that are able to effectively deliver drugs to cells. The possibility of gene silencing using siRNA gives hope for effective treatment of numerous diseases. The aim of this work was to investigate in vitro biophysical properties of dendriplexes formed by siRNA and cationic phosphorus dendrimers of 3rd and 4th generation. First, using the ethidium bromide intercalation method, it was examined whether dendrimers have an ability to form complexes with siRNA. Next, the characterisation of dendriplexes formed at different molar ratios was carried out using biophysical methods. The effects of zeta potential, size and changes of siRNA conformation on the complexation with dendrimers were examined. It was found that both phosphorus dendrimers interacted with siRNA. The zeta potential values of dendriplexes ranged from negative to positive and the hydrodynamic diameter depended on the number of dendrimer molecules in the complex. Furthermore, using circular dichroism spectroscopy it was found that cationic phosphorus dendrimers changed only slightly the shape of siRNA CD spectra, thus they did not induce significant changes in the nucleic acid secondary structure during complex formation. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Review

Jump to: Research

Open AccessReview Molecular Modeling to Study Dendrimers for Biomedical Applications
Molecules 2014, 19(12), 20424-20467; doi:10.3390/molecules191220424
Received: 2 October 2014 / Revised: 12 November 2014 / Accepted: 17 November 2014 / Published: 8 December 2014
Cited by 8 | PDF Full-text (10286 KB) | HTML Full-text | XML Full-text
Abstract
Molecular modeling techniques provide a powerful tool to study the properties of molecules and their interactions at the molecular level. The use of computational techniques to predict interaction patterns and molecular properties can inform the design of drug delivery systems and therapeutic [...] Read more.
Molecular modeling techniques provide a powerful tool to study the properties of molecules and their interactions at the molecular level. The use of computational techniques to predict interaction patterns and molecular properties can inform the design of drug delivery systems and therapeutic agents. Dendrimers are hyperbranched macromolecular structures that comprise repetitive building blocks and have defined architecture and functionality. Their unique structural features can be exploited to design novel carriers for both therapeutic and diagnostic agents. Many studies have been performed to iteratively optimise the properties of dendrimers in solution as well as their interaction with drugs, nucleic acids, proteins and lipid membranes. Key features including dendrimer size and surface have been revealed that can be modified to increase their performance as drug carriers. Computational studies have supported experimental work by providing valuable insights about dendrimer structure and possible molecular interactions at the molecular level. The progress in computational simulation techniques and models provides a basis to improve our ability to better predict and understand the biological activities and interactions of dendrimers. This review will focus on the use of molecular modeling tools for the study and design of dendrimers, with particular emphasis on the efforts that have been made to improve the efficacy of this class of molecules in biomedical applications. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
Open AccessReview The Janus Face of PAMAM Dendrimers Used to Potentially Cure Nonenzymatic Modifications of Biomacromolecules in Metabolic Disorders—A Critical Review of the Pros and Cons
Molecules 2013, 18(11), 13769-13811; doi:10.3390/molecules181113769
Received: 1 July 2013 / Revised: 30 October 2013 / Accepted: 31 October 2013 / Published: 7 November 2013
Cited by 7 | PDF Full-text (6376 KB) | HTML Full-text | XML Full-text
Abstract
Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes [...] Read more.
Diabetes mellitus, which is characterised by high blood glucose levels and the burden of various macrovascular and microvascular complications, is a cause of much human suffering across the globe. While the use of exogenous insulin and other medications can control and sometimes prevent various diabetes-associated sequelae, numerous diabetic complications are still commonly encountered in diabetic patients. Therefore, there is a strong need for safe and effective antihyperglycaemic agents that provide an alternative or compounding option for the treatment of diabetes. In recent years, amino-terminated poly(amido)amine (PAMAM) dendrimers (G2, G3 and G4) have attracted attention due to their protective value as anti-glycation and anti-carbonylation agents that can be used to limit the nonenzymatic modifications of biomacromolecules. The focus of this review is to present a detailed survey of our own data, as well as of the available literature regarding the toxicity, pharmacological properties and overall usefulness of PAMAM dendrimers. This presentation pays particular and primary attention to their therapeutic use in poorly controlled diabetes and its complications, but also in other conditions, such as Alzheimer’s disease, in which such nonenzymatic modifications may underlie the pathophysiological mechanisms. The impact of dendrimer administration on the overall survival of diabetic animals and on glycosylation, glycoxidation, the brain-blood barrier and cellular bioenergetics are demonstrated. Finally, we critically discuss the potential advantages and disadvantages accompanying the use of PAMAM dendrimers in the treatment of metabolic impairments that occur under conditions of chronic hyperglycaemia. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Open AccessReview Dendrimers in Layer-by-Layer Assemblies: Synthesis and Applications
Molecules 2013, 18(7), 8440-8460; doi:10.3390/molecules18078440
Received: 27 June 2013 / Revised: 8 July 2013 / Accepted: 15 July 2013 / Published: 17 July 2013
Cited by 23 | PDF Full-text (587 KB) | HTML Full-text | XML Full-text
Abstract
We review the synthesis of dendrimer-containing layer-by-layer (LbL) assemblies and their applications, including biosensing, controlled drug release, and bio-imaging. Dendrimers can be built into LbL films and microcapsules by alternating deposition of dendrimers and counter polymers on the surface of flat substrates [...] Read more.
We review the synthesis of dendrimer-containing layer-by-layer (LbL) assemblies and their applications, including biosensing, controlled drug release, and bio-imaging. Dendrimers can be built into LbL films and microcapsules by alternating deposition of dendrimers and counter polymers on the surface of flat substrates and colloidal microparticles through electrostatic bonding, hydrogen bonding, covalent bonding, and biological affinity. Dendrimer-containing LbL assemblies have been used to construct biosensors, in which electron transfer mediators and metal nanoparticles are often coupled with dendrimers. Enzymes have been successfully immobilized on the surface of electrochemical and optical transducers by forming enzyme/dendrimer LbL multilayers. In this way, high-performance enzyme sensors are fabricated. In addition, dendrimer LbL films and microcapsules are useful for constructing drug delivery systems because dendrimers bind drugs to form inclusion complexes or the dendrimer surface is covalently modified with drugs. Magnetic resonance imaging of cancer cells by iron oxide nanoparticles coated with dendrimer LbL film is also discussed. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)
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Open AccessReview Dendrimers as Potential Therapeutic Tools in HIV Inhibition
Molecules 2013, 18(7), 7912-7929; doi:10.3390/molecules18077912
Received: 18 June 2013 / Revised: 25 June 2013 / Accepted: 26 June 2013 / Published: 5 July 2013
Cited by 6 | PDF Full-text (458 KB) | HTML Full-text | XML Full-text
Abstract
The present treatments for HIV transfection include chemical agents and gene therapies. Although many chemical drugs, peptides and genes have been developed for HIV inhibition, a variety of non-ignorable drawbacks limited the efficiency of these materials. In this review, we discuss the [...] Read more.
The present treatments for HIV transfection include chemical agents and gene therapies. Although many chemical drugs, peptides and genes have been developed for HIV inhibition, a variety of non-ignorable drawbacks limited the efficiency of these materials. In this review, we discuss the application of dendrimers as both therapeutic agents and non-viral vectors of chemical agents and genes for HIV treatment. On the one hand, dendrimers with functional end groups combine with the gp120 of HIV and CD4 molecule of host cell to suppress the attachment of HIV to the host cell. Some of the dendrimers are capable of intruding into the cell and interfere with the later stages of HIV replication as well. On the other hand, dendrimers are also able to transfer chemical drugs and genes into the host cells, which conspicuously increase the anti-HIV activity of these materials. Dendrimers as therapeutic tools provide a potential treatment for HIV infection. Full article
(This article belongs to the Special Issue Dendrimers in Medicine and Biotechnology)

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