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Selective recognition of anionic cell membranes using targeted liposomes coated with zinc(ii)-bis(dipicolylamine) affinity units.

Turkyilmaz S, Rice DR, Palumbo R, Smith BD - Org. Biomol. Chem. (2014)

Bottom Line: One conjugate (Zn2BDPA-PEG2000-DSPE) was used in liposome formulations doped with the lipophilic near-infrared fluorophore DiR.Fluorescence cell microscopy studies demonstrated that the multivalent liposomes selectively and efficiently target bacteria in the presence of healthy mammalian cells and cause bacterial cell agglutination.The liposomes also exhibited selective staining of the surfaces of dead or dying human cancer cells that had been treated with a chemotherapeutic agent.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall. and University of Notre Dame, Notre Dame, IN 46556, USA. smith.115@nd.edu.

ABSTRACT
Zinc(ii)-bis(dipicolylamine) (Zn2BDPA) coated liposomes are shown to have high recognition selectivity towards vesicle and cell membranes with anionic surfaces. Robust synthetic methods were developed to produce Zn2BDPA-PEG-lipid conjugates with varying PEG linker chain length. One conjugate (Zn2BDPA-PEG2000-DSPE) was used in liposome formulations doped with the lipophilic near-infrared fluorophore DiR. Fluorescence cell microscopy studies demonstrated that the multivalent liposomes selectively and efficiently target bacteria in the presence of healthy mammalian cells and cause bacterial cell agglutination. The liposomes also exhibited selective staining of the surfaces of dead or dying human cancer cells that had been treated with a chemotherapeutic agent.

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Association of a Zn2BDPA coordination complex with a phosphodiester (A), schematic picture of a Zn2BDPA coated liposome with PEG and Zn2BDPA groups on the inner leaflet omitted for clarity (B), structures of Zn2BDPA-lipid conjugates used in this study (C).
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fig1: Association of a Zn2BDPA coordination complex with a phosphodiester (A), schematic picture of a Zn2BDPA coated liposome with PEG and Zn2BDPA groups on the inner leaflet omitted for clarity (B), structures of Zn2BDPA-lipid conjugates used in this study (C).

Mentions: Zinc(ii)-bis(dipicolylamine) (Zn2BDPA) coordination complexes are known to associate with phosphate polyanions in aqueous solution (Fig. 1A) and they have been developed for various supramolecular applications such as optical chemosensing, biomolecule labeling and catalytic hydrolysis.1–21 We have contributed to this effort by demonstrating that Zn2BDPA complexes have selective affinity for anionic cell membrane surfaces over the near-neutral membrane surfaces of healthy mammalian cells.22–28 This discovery has led to molecular imaging probes that can target two types of anionic cell systems with high biomedical significance, namely, bacterial cells and dead/dying mammalian cells. With bacterial cells, the surrounding envelope is anionic because it contains phosphorylated amphiphiles such as phosphatidylglycerol or lipotechoic acid in the case of Gram-positive bacteria, or lipid A in the case of Gram-negative bacteria. With dead/dying mammalian cells, the outer membrane surface becomes anionic due to the exposure of phosphatidylserine during the cell death process. We have shown that fluorescent Zn2BDPA probes can selectively stain these anionic cells even when they are within highly complex and heterogeneous biological environments such as cell culture and living animals.22–28


Selective recognition of anionic cell membranes using targeted liposomes coated with zinc(ii)-bis(dipicolylamine) affinity units.

Turkyilmaz S, Rice DR, Palumbo R, Smith BD - Org. Biomol. Chem. (2014)

Association of a Zn2BDPA coordination complex with a phosphodiester (A), schematic picture of a Zn2BDPA coated liposome with PEG and Zn2BDPA groups on the inner leaflet omitted for clarity (B), structures of Zn2BDPA-lipid conjugates used in this study (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128505&req=5

fig1: Association of a Zn2BDPA coordination complex with a phosphodiester (A), schematic picture of a Zn2BDPA coated liposome with PEG and Zn2BDPA groups on the inner leaflet omitted for clarity (B), structures of Zn2BDPA-lipid conjugates used in this study (C).
Mentions: Zinc(ii)-bis(dipicolylamine) (Zn2BDPA) coordination complexes are known to associate with phosphate polyanions in aqueous solution (Fig. 1A) and they have been developed for various supramolecular applications such as optical chemosensing, biomolecule labeling and catalytic hydrolysis.1–21 We have contributed to this effort by demonstrating that Zn2BDPA complexes have selective affinity for anionic cell membrane surfaces over the near-neutral membrane surfaces of healthy mammalian cells.22–28 This discovery has led to molecular imaging probes that can target two types of anionic cell systems with high biomedical significance, namely, bacterial cells and dead/dying mammalian cells. With bacterial cells, the surrounding envelope is anionic because it contains phosphorylated amphiphiles such as phosphatidylglycerol or lipotechoic acid in the case of Gram-positive bacteria, or lipid A in the case of Gram-negative bacteria. With dead/dying mammalian cells, the outer membrane surface becomes anionic due to the exposure of phosphatidylserine during the cell death process. We have shown that fluorescent Zn2BDPA probes can selectively stain these anionic cells even when they are within highly complex and heterogeneous biological environments such as cell culture and living animals.22–28

Bottom Line: One conjugate (Zn2BDPA-PEG2000-DSPE) was used in liposome formulations doped with the lipophilic near-infrared fluorophore DiR.Fluorescence cell microscopy studies demonstrated that the multivalent liposomes selectively and efficiently target bacteria in the presence of healthy mammalian cells and cause bacterial cell agglutination.The liposomes also exhibited selective staining of the surfaces of dead or dying human cancer cells that had been treated with a chemotherapeutic agent.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall. and University of Notre Dame, Notre Dame, IN 46556, USA. smith.115@nd.edu.

ABSTRACT
Zinc(ii)-bis(dipicolylamine) (Zn2BDPA) coated liposomes are shown to have high recognition selectivity towards vesicle and cell membranes with anionic surfaces. Robust synthetic methods were developed to produce Zn2BDPA-PEG-lipid conjugates with varying PEG linker chain length. One conjugate (Zn2BDPA-PEG2000-DSPE) was used in liposome formulations doped with the lipophilic near-infrared fluorophore DiR. Fluorescence cell microscopy studies demonstrated that the multivalent liposomes selectively and efficiently target bacteria in the presence of healthy mammalian cells and cause bacterial cell agglutination. The liposomes also exhibited selective staining of the surfaces of dead or dying human cancer cells that had been treated with a chemotherapeutic agent.

Show MeSH
Related in: MedlinePlus