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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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Micrographs of human MDA-MB-211 cells treated with cytotoxic etoposide (10 μM) for 16 h and stained with green-emitting PSVue480 (10 μM), and either near-infrared fluorescent untargeted (left column) or Zn2BDPA coated liposomes (right column). (row A) Brightfield; (row B) Green-emission from cells stained with PSVue480; (row C) Near-infrared emission from cells stained with liposomes; (row D) Overlay of A, B, and C. Scale bar = 30 μm.
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fig6: Micrographs of human MDA-MB-211 cells treated with cytotoxic etoposide (10 μM) for 16 h and stained with green-emitting PSVue480 (10 μM), and either near-infrared fluorescent untargeted (left column) or Zn2BDPA coated liposomes (right column). (row A) Brightfield; (row B) Green-emission from cells stained with PSVue480; (row C) Near-infrared emission from cells stained with liposomes; (row D) Overlay of A, B, and C. Scale bar = 30 μm.

Mentions: Standard MTT cell vitality assays showed that the Zn2BDPA coated liposomes were not toxic to MDA-MB-231 human breast cancer cells (Fig. ESI-7†). Furthermore, fluorescence microscopy studies showed that fluorescently labeled Zn2BDPA coated liposomes did not stain healthy MDA-MB-231 cells, but they did stain dead and dying cells that had been treated with a cytotoxic agent. Specifically, MDA-MB-211 cells were incubated with etoposide (10 μM) followed by fluorescent liposomes and PSVue480, a commercially available Zn2BDPA-fluorescein molecular conjugate that has been validated as a green-emitting fluorescent probe that targets exposed PS on the exterior of dead and dying cells. As shown in Fig. 6, the near-infrared Zn2BDPA coated liposomes co-localized with PSVue480. Untargeted liposomes had no affinity for the dead and dying cell population.


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)

Micrographs of human MDA-MB-211 cells treated with cytotoxic etoposide (10 μM) for 16 h and stained with green-emitting PSVue480 (10 μM), and either near-infrared fluorescent untargeted (left column) or Zn2BDPA coated liposomes (right column). (row A) Brightfield; (row B) Green-emission from cells stained with PSVue480; (row C) Near-infrared emission from cells stained with liposomes; (row D) Overlay of A, B, and C. Scale bar = 30 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Micrographs of human MDA-MB-211 cells treated with cytotoxic etoposide (10 μM) for 16 h and stained with green-emitting PSVue480 (10 μM), and either near-infrared fluorescent untargeted (left column) or Zn2BDPA coated liposomes (right column). (row A) Brightfield; (row B) Green-emission from cells stained with PSVue480; (row C) Near-infrared emission from cells stained with liposomes; (row D) Overlay of A, B, and C. Scale bar = 30 μm.
Mentions: Standard MTT cell vitality assays showed that the Zn2BDPA coated liposomes were not toxic to MDA-MB-231 human breast cancer cells (Fig. ESI-7†). Furthermore, fluorescence microscopy studies showed that fluorescently labeled Zn2BDPA coated liposomes did not stain healthy MDA-MB-231 cells, but they did stain dead and dying cells that had been treated with a cytotoxic agent. Specifically, MDA-MB-211 cells were incubated with etoposide (10 μM) followed by fluorescent liposomes and PSVue480, a commercially available Zn2BDPA-fluorescein molecular conjugate that has been validated as a green-emitting fluorescent probe that targets exposed PS on the exterior of dead and dying cells. As shown in Fig. 6, the near-infrared Zn2BDPA coated liposomes co-localized with PSVue480. Untargeted liposomes had no affinity for the dead and dying cell population.

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