Document Detail

Dendrimer-Based Multivalent Vancomycin Nanoplatform for Targeting the Drug-Resistant Bacterial Surface.
MedLine Citation:
PMID:  23259666     Owner:  NLM     Status:  Publisher    
Vancomycin represents the preferred ligand for bacteria-targeting nanosystems. However, it is inefficient for emerging vancomycin-resistant species because of its poor affinity to the reprogrammed cell wall structure. This study demonstrates the use of a multivalent strategy as an effective way for overcoming such an affinity limitation in bacteria targeting. We designed a series of fifth generation (G5) poly(amidoamine) (PAMAM) dendrimers tethered with vancomycin at the C-terminus at different valencies. We performed surface plasmon resonance (SPR) studies to determine their binding avidity to two cell wall models, each made with either a vancomycin-susceptible (d)-Ala-(d)-Ala or vancomycin-resistant (d)-Ala-(d)-Lac cell wall precursor. These conjugates showed remarkable enhancement in avidity in the cell wall models tested, including the vancomycin-resistant model, which had an increase in avidity of four to five orders of magnitude greater than free vancomycin. The tight adsorption of the conjugate to the model surface corresponded with its ability to bind vancomycin-susceptible Staphylococcus aureus bacterial cells in vitro as imaged by confocal fluorescent microscopy. This vancomycin platform was then used to fabricate the surface of iron oxide nanoparticles by coating them with the dendrimer conjugates, and the resulting dendrimer-covered magnetic nanoparticles were demonstrated to rapidly sequester bacterial cells. In summary, this article investigates the biophysical basis of the tight, multivalent association of dendrimer-based vancomycin conjugates to the bacterial cell wall, and proposes a potential new use of this nanoplatform in targeting Gram-positive bacteria.
Seok Ki Choi; Andrzej Myc; Justin Ezekiel Silpe; Madhuresh Sumit; Pamela Tinmoi Wong; Kelly McCarthy; Ankur M Desai; Thommey P Thomas; Alina Kotlyar; Mark M Banaszak Holl; Bradford G Orr; James R Baker
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-24
Journal Detail:
Title:  ACS nano     Volume:  -     ISSN:  1936-086X     ISO Abbreviation:  ACS Nano     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101313589     Medline TA:  ACS Nano     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Internal Medicine, ‡Michigan Nanotechnology Institute for Medicine and Biological Sciences, §Department of Macromolecular Science and Engineering, ⊥Program in Biomedical Sciences, ¶Department of Chemistry, and #Department of Physics, University of Michigan , Ann Arbor, Michigan 48109, United States, ∥Department of Immunology of Infectious Diseases, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy , Polish Academy of Sciences, Wroclaw, Poland.
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