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2. ANTIBODY-DRUG CONJUGATE THERAPY AGAINST S. AUREUS IMPLANT-ASSOCIATED INFECTION IN A MURINE MODEL

Author

Tvilum, Anne, primary, Johansen, Mikkel Illemann, additional, Glud, Lærke, additional, Malskær, Diana, additional, Khamas, Amanda, additional, Carmali, Sheiliza, additional, Mhatre, Snehit, additional, Søgaard, Ane, additional, Faddy, Emma, additional, de Vor, Lisanne, additional, Rooijakkers, Suzan, additional, Østergaard, Lars, additional, Meyer, Rikke, additional, Zelikin, Alexander, additional, and Jørgensen, Nis, additional

Published
2023
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4. Antibody-Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release

Author

Tvilum, Anne Selch, Johansen, Mikkel Illemann, Glud, Lærke Nøhr, Ivarsen, Diana Malskær, Khamas, Amanda Batoul, Carmali, Sheiliza, Mhatre, Snehit Satish, Søgaard, Ane Bretschneider, Faddy, Emma, de Vor, Lisanne, H. M. Rooijakkers, Suzan, Østergaard, Lars, Jørgensen, Nis Pedersen, Meyer, Rikke Louise, and Zelikin, Alexander

Abstract

The treatment of implant-associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune system and harbor antibiotic-tolerant persister cells. This need is addressed herein through an engineering of antibody-drug conjugates (ADCs) that contain an anti-neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non-specific counterpart, in suspension and within biofilms, in vitro, and in an implant-associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms.

Published
2023

5. Antibody‐Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release

Author

Tvilum, Anne, primary, Johansen, Mikkel I., additional, Glud, Lærke N., additional, Ivarsen, Diana M., additional, Khamas, Amanda B., additional, Carmali, Sheiliza, additional, Mhatre, Snehit Satish, additional, Søgaard, Ane B., additional, Faddy, Emma, additional, de Vor, Lisanne, additional, Rooijakkers, Suzan H. M., additional, Østergaard, Lars, additional, Jørgensen, Nis P., additional, Meyer, Rikke L., additional, and Zelikin, Alexander N., additional

Published
2023
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6. Antibody-drug conjugates to treat bacterial biofilms

Author

Tvilum, Anne, primary, Johansen, Mikkel I., additional, Glud, Lærke N., additional, Ivarsen, Diana M., additional, Khamas, Amanda B., additional, Carmali, Sheiliza, additional, Mhatre, Snehit Satish, additional, Søgaard, Ane B., additional, Faddy, Emma, additional, de Vor, Lisanne, additional, Rooijakkers, Suzan H.M., additional, Østergaard, Lars, additional, Jørgensen, Nis P., additional, Meyer, Rikke L., additional, and Zelikin, Alexander N., additional

Published
2023
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9. Efficient Wet Adhesion through Mussel‐Inspired Proto‐Coacervates.

Author

Huynh, Tan‐Phat, Chen, Yaqing, Bach‐Gansmo, Fiona L., Dehli, Jeppe, Ibsen, Vicki N., Foss, Morten, Tvilum, Anne S., Zelikin, Alexander N., and Birkedal, Henrik

Subjects
ORGANIC solvents, PHASE separation, ELECTROSTATIC interaction, DOPA, COACERVATION, GLUE, ADHESIVES, BIOMEDICAL adhesives
Abstract

Adhesion underwater is a major challenge. Mussel‐inspired complex coacervates functionalized with L‐3,4‐dihydroxyphenylalanine (L‐DOPA) are proposed for underwater adhesives through versatile chemistry of DOPA, however, simple, efficient, controllable, and nontoxic procedures to harness them are still under investigation. In this study, inspired from the mussel byssus formation process, coacervate adhesives are formed underwater by simple injection of an acidic proto‐coacervate of DOPA functionalized polyelectrolytes on underwater surfaces. The proto‐coacervate is initially an acidic liquid, it increased in pH due to water diffusion, resulting in coacervation driven by electrostatic interaction, without the requirement for pH adjustment or organic solvents. Additionally, the pH of liquid–liquid phase separation is tuned by substituting polyelectrolytes with different pKa, which satisfied different pH requirement in real life. The coacervate‐based adhesives on glass substrates exhibit strengths comparable to commercial glues when dry and to mussel glue when wet, showing high biocompatibility in human epidermis in vitro. [ABSTRACT FROM AUTHOR]

Published
2023
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