Limits...
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.

Show MeSH

Related in: MedlinePlus

Four strains of pelleted bacteria after treatment with fluorescent untargeted liposomes (left column) or fluorescent Zn2BDPA coated liposomes (right column) and imaged using a CCD camera. (A) Brightfield; (B) near-infrared fluorescence; (C) merge. 1 = E. coli, 2 = P. aeruginosa, 3 = S. aureus and 4 = K. pneumoniae. Scale bar indicates near-infrared emission intensity for both fluorescence images in row B.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4128505&req=5

fig3: Four strains of pelleted bacteria after treatment with fluorescent untargeted liposomes (left column) or fluorescent Zn2BDPA coated liposomes (right column) and imaged using a CCD camera. (A) Brightfield; (B) near-infrared fluorescence; (C) merge. 1 = E. coli, 2 = P. aeruginosa, 3 = S. aureus and 4 = K. pneumoniae. Scale bar indicates near-infrared emission intensity for both fluorescence images in row B.

Mentions: The bacterial targeting of Zn2BDPA coated liposomes was evaluated by conducting imaging experiments using cultures of E. coli, P. aeruginosa, S. aureus, and K. pneumoniae. In each case, separate samples of bacteria (∼108 cells) were treated for 15 min with Zn2BDPA coated liposomes (Zn2BDPA-PEG2000-DSPE–DiR–cholesterol–POPC, 2 : 2 : 30 : 66) or untargeted liposomes (DiR–cholesterol–POPC, 2 : 30 : 68). The treated cells were pelleted by microcentrifugation and the tubes were imaged using a CCD camera. As shown in Fig. 3, the fluorescent Zn2BDPA coated liposomes were located primarily in the bacterial pellet, whereas, the fluorescent untargeted liposomes were primarily in the supernatant above the pellet. After pellet imaging, the bacterial cells were rinsed twice, dispersed into solution by vortexing, and subjected to fluorescence microscopy. Shown in Fig. 4 are typical micrographs of cross-linked bacteria/liposome aggregates. Analogous micrographs of the pelleted bacteria that had been treated with fluorescent untargeted liposomes showed no evidence for bacterial cross-linking (Fig. ESI-6†).


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)

Four strains of pelleted bacteria after treatment with fluorescent untargeted liposomes (left column) or fluorescent Zn2BDPA coated liposomes (right column) and imaged using a CCD camera. (A) Brightfield; (B) near-infrared fluorescence; (C) merge. 1 = E. coli, 2 = P. aeruginosa, 3 = S. aureus and 4 = K. pneumoniae. Scale bar indicates near-infrared emission intensity for both fluorescence images in row B.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Four strains of pelleted bacteria after treatment with fluorescent untargeted liposomes (left column) or fluorescent Zn2BDPA coated liposomes (right column) and imaged using a CCD camera. (A) Brightfield; (B) near-infrared fluorescence; (C) merge. 1 = E. coli, 2 = P. aeruginosa, 3 = S. aureus and 4 = K. pneumoniae. Scale bar indicates near-infrared emission intensity for both fluorescence images in row B.
Mentions: The bacterial targeting of Zn2BDPA coated liposomes was evaluated by conducting imaging experiments using cultures of E. coli, P. aeruginosa, S. aureus, and K. pneumoniae. In each case, separate samples of bacteria (∼108 cells) were treated for 15 min with Zn2BDPA coated liposomes (Zn2BDPA-PEG2000-DSPE–DiR–cholesterol–POPC, 2 : 2 : 30 : 66) or untargeted liposomes (DiR–cholesterol–POPC, 2 : 30 : 68). The treated cells were pelleted by microcentrifugation and the tubes were imaged using a CCD camera. As shown in Fig. 3, the fluorescent Zn2BDPA coated liposomes were located primarily in the bacterial pellet, whereas, the fluorescent untargeted liposomes were primarily in the supernatant above the pellet. After pellet imaging, the bacterial cells were rinsed twice, dispersed into solution by vortexing, and subjected to fluorescence microscopy. Shown in Fig. 4 are typical micrographs of cross-linked bacteria/liposome aggregates. Analogous micrographs of the pelleted bacteria that had been treated with fluorescent untargeted liposomes showed no evidence for bacterial cross-linking (Fig. ESI-6†).

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