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Publications (10 of 127) Show all publications
Andrén, O. C. J., Ingverud, T., Hult, D., Håkansson, J., Bogestål, Y., Caous, J. S., . . . Malkoch, M. (2019). Antibiotic-Free Cationic Dendritic Hydrogels as Surgical-Site-Infection-Inhibiting Coatings. Advanced Healthcare Materials, 8(5)
Open this publication in new window or tab >>Antibiotic-Free Cationic Dendritic Hydrogels as Surgical-Site-Infection-Inhibiting Coatings
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2019 (English)In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 8, no 5Article in journal (Refereed) Published
Abstract [en]

Abstract A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged ?-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G? = 0.5?8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.

Place, publisher, year, edition, pages
John Wiley & Sons, Ltd, 2019
Keywords
antibacterial, dendrimer, hydrogels, surgical-site infection
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-249169 (URN)10.1002/adhm.201801619 (DOI)000461575200014 ()2-s2.0-85061270456 (Scopus ID)
Note

QC 20190412

Available from: 2019-04-11 Created: 2019-04-11 Last updated: 2019-04-12Bibliographically approved
Nordstrom, R., Andrén, O. C. J., Singh, S., Malkoch, M., Davoudi, M., Schmidtchen, A. & Malmsten, M. (2019). Degradable dendritic nanogels as carriers for antimicrobial peptides. Journal of Colloid and Interface Science, 554, 592-602
Open this publication in new window or tab >>Degradable dendritic nanogels as carriers for antimicrobial peptides
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2019 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 554, p. 592-602Article in journal (Refereed) Published
Abstract [en]

In the present study, we investigate degradable anionic dendritic nanogels (DNG) as carriers for antimicrobial peptides (AMPS). In such systems, the dendritic part contains carboxylic acid-based anionic binding sites for cationic AMPs, whereas linear poly(ethylene glycol) (PEG) chains form a shell for promotion of biological stealth. In order to clarify factors influencing membrane interactions of such systems, we here address effects of nanogel charge, cross-linking, and degradation on peptide loading/release, as well as consequences of these factors for lipid membrane interactions and antimicrobial effects. The DNGs were found to bind the AMPs LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES) and DPK-060 (GKHKNKGKKNGKHNGWKWWW). For the smaller DPK-060 peptide, loading was found to increase with increasing nanogel charge density. For the larger LL-37, on the other hand, peptide loading was largely insensitive to nanogel charge density. In line with this, results on the secondary structure, as well as on the absence of stabilization from proteolytic degradation by the nanogels, show that the larger LL-37 is unable to enter into the interior of the nanogels. While 40-60% nanogel degradation occurred over 10 days, promoted at high ionic strength and lower cross-linking density/higher anionic charge content, peptide release at physiological ionic strength was substantially faster, and membrane destabilization not relying on nanogel degradation. Ellipsometry and liposome leakage experiments showed both free peptide and peptide/DNG complexes to cause membrane destabilization, indicated also by antimicrobial activities being comparable for nanogel-bound and free peptide. Finally, the DNGs were demonstrated to display low toxicity towards erythrocytes even at peptide concentrations of 100 mu M.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE, 2019
Keywords
Antimicrobial peptide, Degradable, Dendritic, Hyperbranched drug delivery, Membrane, Nanogel
National Category
Physical Chemistry
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-261938 (URN)10.1016/j.jcis.2019.07.028 (DOI)000487346200061 ()31330426 (PubMedID)2-s2.0-85069570924 (Scopus ID)
Note

QC 20191015

Available from: 2019-10-15 Created: 2019-10-15 Last updated: 2019-11-26Bibliographically approved
Ingverud, T. & Malkoch, M. (2019). Helux: A Heterofunctional Hyperbranched Poly(amido amine) Carboxylate. ACS APPLIED POLYMER MATERIALS, 1(7), 1845-1853
Open this publication in new window or tab >>Helux: A Heterofunctional Hyperbranched Poly(amido amine) Carboxylate
2019 (English)In: ACS APPLIED POLYMER MATERIALS, ISSN 2637-6105, Vol. 1, no 7, p. 1845-1853Article in journal (Refereed) Published
Abstract [en]

Herein we present the first scientific report on the commercially available Helux 33/16 - a heterofunctional poly(amido amine carboxylate) hyperbranched polymer (Native Helux). The Native Helux, built from diethyl maleate (DEM) and diaminohexane (HMDA), was characterized, in part aided by reverse engineering of a similar scaffold with the same monomers. Different purification methods resulted in higher molecular weight polymers ranging from 8.4 to 51.7 kDa (M-w), and the Helux considered the purest, having 10 mmol (primary and secondary amines)/g as well as 2-4 mmol carboxylic/g Helux. Additionally, aqueous-mediated postmodifications of Helux were achieved including Michael addition, guanylation, and ring-opening of sultone, as well as water/ethyl acetate-mediated amidation of imidazole-activated pentenoic acid. The inherent heterofunctionality of Helux, amines and carboxylic groups, was further explored by a one-component self-cross-linking approach that yielded a dendritic poly(amido amine) network with autofluorescence-exhibiting properties and a T-g of 59 degrees C. The Helux network exhibited a storage modulus (G') of 7.9 MPa at 25 degrees C and in dry state, and 0.9 MPa (G') when plasticized by 50 wt % swelling (in water) of the network. Finally, dendritic hydrogels based on Helux were produced by a spontaneous NHS-amidation reaction with difunctional 10kPEG-NHS. The mechanical properties of the hydrogels were found to be dependent on the curing temperature for the hydrogel, yielding a G' of 8 and 14.5 kPa, a stress at break of 11.5 and 22.7 kPa, and a strain-at-break of 161 and 163%, at 25 and 37 degrees C, respectively.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2019
Keywords
commercial, heterofunctional, hyperbranched, polyampholyte, postfunctionalization, self-cross-linking, hydrogel
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-256273 (URN)10.1021/acsapm.9b00364 (DOI)000476967100025 ()
Note

QC 20191029

Available from: 2019-10-29 Created: 2019-10-29 Last updated: 2019-10-29Bibliographically approved
Zhang, Y., Andrén, O. C. J., Nordström, R., Fan, Y., Malmsten, M., Mongkhontreerat, S. & Malkoch, M. (2019). Off-Stoichiometric Thiol-Ene Chemistry to Dendritic Nanogel Therapeutics. Advanced Functional Materials, 29(18), Article ID 1806693.
Open this publication in new window or tab >>Off-Stoichiometric Thiol-Ene Chemistry to Dendritic Nanogel Therapeutics
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2019 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 29, no 18, article id 1806693Article in journal (Refereed) Published
Abstract [en]

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. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Place, publisher, year, edition, pages
Wiley-VCH Verlag, 2019
Keywords
cancer treatment, dendritic nanogel, drug delivery, nanomedicine, 3D modeling, Biocompatibility, Controlled drug delivery, Medical nanotechnology, Oncology, Self assembly, Targeted drug delivery, Core functionality, Diffusion controlled, Linear dendritic, Master batch, Nanogels, Therapeutic efficacy, Thiol-ene chemistries, Toxic side effects, Nanostructured materials
National Category
Materials Chemistry
Identifiers
urn:nbn:se:kth:diva-252526 (URN)10.1002/adfm.201806693 (DOI)000471330500004 ()2-s2.0-85062732882 (Scopus ID)
Note

QC 20190605

Available from: 2019-06-05 Created: 2019-06-05 Last updated: 2019-10-28Bibliographically approved
Rozenbaum, R. T., Andrén, O. C. J., van der Mei, H. C., Woudstra, W., Busscher, H. J., Malkoch, M. & Sharma, P. K. (2019). Penetration and Accumulation of Dendrons with Different Peripheral Composition in Pseudomonas aeruginosa Biofilms. Nano letters (Print), 19(7), 4327-4333
Open this publication in new window or tab >>Penetration and Accumulation of Dendrons with Different Peripheral Composition in Pseudomonas aeruginosa Biofilms
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2019 (English)In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 19, no 7, p. 4327-4333Article in journal (Refereed) Published
Abstract [en]

Multidrug resistant bacterial infections threaten to become the number one cause of death by the year 2050. Development of antimicrobial dendritic polymers is considered promising as an alternative infection control strategy. For antimicrobial dendritic polymers to effectively kill bacteria residing in infectious biofilms, they have to penetrate and accumulate deep into biofilms. Biofilms are often recalcitrant to antimicrobial penetration and accumulation. Therefore, this work aims to determine the role of compact dendrons with different peripheral composition in their penetration into Pseudomonas aeruginosa biofilms. Red fluorescently labeled dendrons with pH-responsive NH3+ peripheral groups initially penetrated faster from a buffer suspension at pH 7.0 into the acidic environment of P. aeruginosa biofilms than dendrons with OH or COO- groups at their periphery. In addition, dendrons with NH3+ peripheral groups accumulated near the top of the biofilm due to electrostatic double-layer attraction with negatively charged biofilm components. However, accumulation of dendrons with OH and COO- peripheral groups was more evenly distributed across the depth of the biofilms than NH3+ composed dendrons and exceeded accumulation of NH3+ composed dendrons after 10 min of exposure. Unlike dendrons with NH3+ groups at their periphery, dendrons with OH or COO- peripheral groups, lacking strong electrostatic double-layer attraction with biofilm components, were largely washed-out during exposure to PBS without dendrons. Thus, penetration and accumulation of dendrons into biofilms is controlled by their peripheral composition through electrostatic double-layer interactions, which is an important finding for the further development of new antimicrobial or antimicrobial-carrying dendritic polymers.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019
Keywords
Nanomedicine, nanocarriers, nanotechnology, dendrimers, dendritic polymers
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-255568 (URN)10.1021/acs.nanolett.9b00838 (DOI)000475533900015 ()31142116 (PubMedID)2-s2.0-85067935225 (Scopus ID)
Note

QC 20190802

Available from: 2019-08-02 Created: 2019-08-02 Last updated: 2019-10-04Bibliographically approved
Latorre-Sanchez, A., Johansson, M., Zhang, Y., Malkoch, M. & Pomposo, J. A. (2018). Active quinine-based films able to release antimicrobial compounds via melt quaternization at low temperature. Journal of materials chemistry. B, 6(1), 98-104
Open this publication in new window or tab >>Active quinine-based films able to release antimicrobial compounds via melt quaternization at low temperature
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2018 (English)In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 6, no 1, p. 98-104Article in journal (Refereed) Published
Abstract [en]

The fabrication of antibacterial films based on renewable materials (e.g., chitosan) has attracted significant interest in fields such as food packaging, health care and medicine. However, exploiting the antibacterial properties of cinchona alkaloids to design active nanostructured films able to release quinine-based antimicrobial compounds has not been considered previously. Herein, we develop two different routes to produce active quinine-based nanostructured cross-linked films by exploiting the multiple reactive sites of quinine and, specifically, both the nitrogen atom and the vinyl group of the quinuclidine portion of the molecule, as well as their corresponding orthogonal quaternization and thiol-ene coupling reactions. The first synthetic strategy produces stiff and brittle nanostructured quinine-based films of limited utility for practical applications. Conversely, the second approach produces active, flexible and nanostructured quinine-based films (T-g = - 14 degrees C, Young's modulus = 1.3 GPa), which are able to release antimicrobial compounds against E. coli that, remarkably, are noncytotoxic against mouse macrophage and human dermal fibroblast cells. These kinds of active cinchona alkaloid-based coatings are easy to prepare by means of simple, solvent-free, melt quaternization/spreading procedures at a relatively low temperature (120 degrees C), making this second approach one of the most facile reported procedures to date to produce active nanostructured bio-based films.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2018
National Category
Polymer Technologies
Identifiers
urn:nbn:se:kth:diva-220813 (URN)10.1039/c7tb02739g (DOI)000418379700009 ()2-s2.0-85038944460 (Scopus ID)
Note

QC 20180116

Available from: 2018-01-16 Created: 2018-01-16 Last updated: 2018-03-13Bibliographically approved
Hult, D., Garcia-Gallego, S., Ingverud, T., Andrén, O. & Malkoch, M. (2018). Degradable High Tg Sugar Derived Polycarbonates from Isosorbide and Dihydroxyacetone. Polymer Chemistry, 9(17), 2238-2246
Open this publication in new window or tab >>Degradable High Tg Sugar Derived Polycarbonates from Isosorbide and Dihydroxyacetone
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2018 (English)In: Polymer Chemistry, ISSN 1759-9954, E-ISSN 1759-9962, Vol. 9, no 17, p. 2238-2246Article in journal (Refereed) Published
Abstract [en]

Polycarbonates from isosorbide and dihydroxyacetone (DHA) have been synthesised using organocatalytic step-growth polymerization of their corresponding diols and bis-carbonylimidazolides monomers. By choice of feed ratio and monomer activation, either isosorbide or ketal protected DHA, random and alternating poly(Iso-co-DHA) carbonates have been formed. Thermal properties by DSC and TGA were herein strongly correlated to monomer composition. Dilution studies using 1H-NMR of a model compound DHA-diethyl carbonate in acetonitrile and deuterated water highlighted the influence of α-substituents on the keto/hydrate equilibrium of DHA. Further kinetics studies of in the pH* range of 4.7 to 9.6 serve to show the hydrolytic pH-profile of DHA-carbonates. The Hydrolytic degradation of deprotected polymer pellets show an increased degradation with increasing DHA content. Pellets with a random or alternating configuration show different characteristics in terms of mass loss and molecular weight loss profile over time.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2018
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-224753 (URN)10.1039/C8PY00256H (DOI)000431183700004 ()2-s2.0-85046299922 (Scopus ID)
Funder
Swedish Research Council, 2011-5358 2010-435 2015-04779Knut and Alice Wallenberg Foundation, 2012-0196
Note

QC 20180322

Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2019-10-10Bibliographically approved
Martin-Serrano Ortiz, A., Stenström, P., Antunez, P. M., Andrén, O. C. J., Torres, M. J., Montanez, M. I. & Malkoch, M. (2018). Design of multivalent fluorescent dendritic probes for site-specific labeling of biomolecules. Journal of Polymer Science Part A: Polymer Chemistry, 56(15), 1609-1616
Open this publication in new window or tab >>Design of multivalent fluorescent dendritic probes for site-specific labeling of biomolecules
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2018 (English)In: Journal of Polymer Science Part A: Polymer Chemistry, ISSN 0887-624X, E-ISSN 1099-0518, Vol. 56, no 15, p. 1609-1616Article in journal (Refereed) Published
Abstract [en]

Herein, the synthesis and characterization of orthogonal dendrons decorated with multiple units of fluorescent and a chemoselective group at a focal point, followed by specific antibody labeling, is presented. Fluorescence results confirm the applicability of the fluorescent probes for biomolecule labeling and fluorescent signal amplification.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
antibodies, click chemistry, conjugation chemistry, dendrimers, dyes, fluorescence, imaging, multivalent labeling, polyester dendrons, selectivity
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-232228 (URN)10.1002/pola.29055 (DOI)000436543800001 ()2-s2.0-85049074485 (Scopus ID)
Funder
Knut and Alice Wallenberg Foundation, 2012-0196
Note

QC 20180720

Available from: 2018-07-20 Created: 2018-07-20 Last updated: 2019-10-09Bibliographically approved
Stenström, P., Manzanares, D., Zhang, Y., Ceña, V. & Malkoch, M. (2018). Evaluation of amino-functional polyester dendrimers based on Bis-MPA as nonviral vectors for siRNA delivery. Molecules, 23(8), Article ID 2028.
Open this publication in new window or tab >>Evaluation of amino-functional polyester dendrimers based on Bis-MPA as nonviral vectors for siRNA delivery
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2018 (English)In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 23, no 8, article id 2028Article in journal (Refereed) Published
Abstract [en]

Herein, we present the first evaluation of cationic dendrimers based on 2,2-bis(methylol)propionic acid (bis-MPA) as nonviral vectors for transfection of short interfering RNA (siRNA) in cell cultures. The study encompassed dendrimers of generation one to four (G1-G4), modified to bear 6-48 amino end-groups, where the G2-G4 proved to be capable of siRNA complexation and protection against RNase-mediated degradation. The dendrimers were nontoxic to astrocytes, glioma (C6), and glioblastoma (U87), while G3 and G4 exhibited concentration dependent toxicity towards primary neurons. The G2 showed no toxicity to primary neurons at any of the tested concentrations. Fluorescence microscopy experiments suggested that the dendrimers are highly efficient at endo-lysosomal escape since fluorescently labeled dendrimers were localized specifically in mitochondria, and diffuse cytosolic distribution of fluorescent siRNA complexed by dendrimers was observed. This is a desired feature for intracellular drug delivery, since the endocytic pathway otherwise transfers the drugs into lysosomes where they can be degraded without reaching their intended target. siRNA-transfection was successful in C6 and U87 cell lines using the G3 and G4 dendrimers followed by a decrease of approximately 20% of target protein p42-MAPK expression.

Place, publisher, year, edition, pages
MDPI AG, 2018
Keywords
Bis-MPA, Dendrimer, Monodisperse, Polycation, RNAi, SiRNA
National Category
Polymer Chemistry
Identifiers
urn:nbn:se:kth:diva-238030 (URN)10.3390/molecules23082028 (DOI)000445295500193 ()2-s2.0-85053600476 (Scopus ID)
Note

Export Date: 30 October 2018; Article; CODEN: MOLEF; Correspondence Address: Malkoch, M.; Fiber and Polymer Technology, KTH Royal Institute of TechnologySweden; email: malkoch@kth.se

QC 20190115

Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-01-15Bibliographically approved
Granskog, V., Garcia-Gallego, S., von Kieseritzky, J., Pettersson, J., Stenlund, P., Zhang, Y., . . . Malkoch, M. (2018). High-performance and biocompatible thiol-ene based adhesive for bone fracture fixation. Paper presented at 256th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nanoscience, Nanotechnology and Beyond, AUG 19-23, 2018, Boston, MA. Abstract of Papers of the American Chemical Society, 256
Open this publication in new window or tab >>High-performance and biocompatible thiol-ene based adhesive for bone fracture fixation
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2018 (English)In: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 256Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2018
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-238547 (URN)000447609105053 ()
Conference
256th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nanoscience, Nanotechnology and Beyond, AUG 19-23, 2018, Boston, MA
Note

QC 20181105

Available from: 2018-11-05 Created: 2018-11-05 Last updated: 2018-11-05Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-9200-8004

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