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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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Cross-linking of liposomes containing Zn2BDPA-PEG2000-DSPE and anionic target liposomes containing POPS. (A) Liposomes composed of Zn2BDPA-PEG2000-DSPE–cholesterol–POPC (2.5 : 30 : 67.5 mol%, 0.83 μmol total lipid) in zinc-containing HEPES buffer. (B) Liposomes composed of POPS–cholesterol–POPC (10 : 30 : 60 mol%, 0.83 μmol total lipid) in zinc-containing HEPES buffer. (C) Admixture of liposome samples A and B.
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fig2: Cross-linking of liposomes containing Zn2BDPA-PEG2000-DSPE and anionic target liposomes containing POPS. (A) Liposomes composed of Zn2BDPA-PEG2000-DSPE–cholesterol–POPC (2.5 : 30 : 67.5 mol%, 0.83 μmol total lipid) in zinc-containing HEPES buffer. (B) Liposomes composed of POPS–cholesterol–POPC (10 : 30 : 60 mol%, 0.83 μmol total lipid) in zinc-containing HEPES buffer. (C) Admixture of liposome samples A and B.

Mentions: The selective affinity of Zn2BDPA coated liposomes for anionic membranes was vividly demonstrated by conducting experiments that mixed liposomes composed of Zn2BDPA-PEG2000-DSPE–cholesterol–POPC (2.5 : 30 : 67.5) with target liposomes of various compositions. As shown in Fig. 2, mixing with anionic liposomes composed of POPS–cholesterol–POPC (10 : 30 : 60) resulted in rapid and extensive precipitation. Mixing with anionic liposomes composed of DPPG–cholesterol–POPC (10 : 30 : 60) produced the same outcome (see ESI†). In contrast, mixing with uncharged liposomes composed of cholesterol–POPC (30 : 70) produced no precipitation. Control experiments showed that the anionic liposome systems do not form aggregates when exposed to Zn(NO3)2 alone, thus confirming that the Zn2BDPA affinity units are essential for the anionic membrane recognition process. These favorable liposome targeting results encouraged us to conduct cell recognition studies using both human and bacterial cells. The liposomes were doped with a small amount of the near-infrared fluorescent lipophilic dye, DiR, to enable effective visualization using fluorescence microscopy.


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)

Cross-linking of liposomes containing Zn2BDPA-PEG2000-DSPE and anionic target liposomes containing POPS. (A) Liposomes composed of Zn2BDPA-PEG2000-DSPE–cholesterol–POPC (2.5 : 30 : 67.5 mol%, 0.83 μmol total lipid) in zinc-containing HEPES buffer. (B) Liposomes composed of POPS–cholesterol–POPC (10 : 30 : 60 mol%, 0.83 μmol total lipid) in zinc-containing HEPES buffer. (C) Admixture of liposome samples A and B.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Cross-linking of liposomes containing Zn2BDPA-PEG2000-DSPE and anionic target liposomes containing POPS. (A) Liposomes composed of Zn2BDPA-PEG2000-DSPE–cholesterol–POPC (2.5 : 30 : 67.5 mol%, 0.83 μmol total lipid) in zinc-containing HEPES buffer. (B) Liposomes composed of POPS–cholesterol–POPC (10 : 30 : 60 mol%, 0.83 μmol total lipid) in zinc-containing HEPES buffer. (C) Admixture of liposome samples A and B.
Mentions: The selective affinity of Zn2BDPA coated liposomes for anionic membranes was vividly demonstrated by conducting experiments that mixed liposomes composed of Zn2BDPA-PEG2000-DSPE–cholesterol–POPC (2.5 : 30 : 67.5) with target liposomes of various compositions. As shown in Fig. 2, mixing with anionic liposomes composed of POPS–cholesterol–POPC (10 : 30 : 60) resulted in rapid and extensive precipitation. Mixing with anionic liposomes composed of DPPG–cholesterol–POPC (10 : 30 : 60) produced the same outcome (see ESI†). In contrast, mixing with uncharged liposomes composed of cholesterol–POPC (30 : 70) produced no precipitation. Control experiments showed that the anionic liposome systems do not form aggregates when exposed to Zn(NO3)2 alone, thus confirming that the Zn2BDPA affinity units are essential for the anionic membrane recognition process. These favorable liposome targeting results encouraged us to conduct cell recognition studies using both human and bacterial cells. The liposomes were doped with a small amount of the near-infrared fluorescent lipophilic dye, DiR, to enable effective visualization using fluorescence microscopy.

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