Saccharide‐assisted delivery of cytotoxic liposomes to human malignant cells

Водовозова, Е. Л.; Gayenko, Galina P.; Razinkov, Vladimir I.; Korchagina, Elena; Бовин, Н. В.; Molotkovsky, Julian G.

doi:10.1080/15216549800201582

Cited by 3 publications

(1 citation statement)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specificantibodies have beenutilized to selectivelyinhibit an E-selectin mediatedadhesion. Theyare used as solution (15,31,32) or attached to the surfaceofliposomes (17,20,33). Alternatively,ligandswith the carbohydratestructureofthe sialyl Lewis XorA type,which compete with the same ligands expressed by tumor cells for ab indingt oe ndothelial selectin (34,35) have beenusedfor liposomal approaches (18)(19)(20).Incomparison to solved ligands, ligands attached to the surfaceofliposomalcarriers provide the advantage to enable amultivalent binding becauseoftheir ability to formclusters of ligandsatthe liposomal surface.…”

Section: Discussionmentioning

confidence: 99%

Effect of surface modified liposomes on the aggregation of platelets and tumor cells

Keil¹,

Zeisig²,

Fichtner³

2005

Thromb Haemost

View full text Add to dashboard Cite

Metastasis is still the most serious reason for the high mortality of cancer patients. It is a complex process in which platelets play a crucial role. Several attempts have been performed to inhibit the metastatic process, some of these using modified liposomes. The aggregation behaviour of human platelets and HT29 colon carcinoma cells in the presence of liposomes with a modified surface has been investigated in the present study. Liposomes (PC/CH/DMPE) were unmodified, sterically stabilized by polyethylene glycol (PEG-DSPE), or equipped with the carbohydrate ligand sialyl Lewis(X) (conjugated to PEG-DMPE or DMPE as anchor) intended to specifically compete with ligands expressed by HT29 cells. We found in vitro that an addition of surface modified liposomes to human platelets in plasma caused an up to 2.9-fold increase in platelet aggregation. In addition, when HT29 tumor cells were mixed with platelets and surface modified liposomes, the number of tumor cells found in aggregates increased significantly from 8.3 % (only tumor cells) to 30.2 %. This result was supported by fluorescence micrographs demonstrating a strong association of platelets and liposomes around the tumor cells. In addition, a clear decrease in number and a change in the distribution of metastases after intravenous injection of HT29 cells in combination with liposomes was observed in vivo. While in control mice metastases in lung, liver and in intestine were prevailing, liposomal treatment resulted in a new localization of metastases in muscles. Taking together, the ability of surface modified liposomes to enhance aggregate formation of platelets and tumor cells has been demonstrated for the first time. The capability of these vesicles to interfere with the metastatic process might have implications for the use of such liposomes for therapeutic applications.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of surface modified liposomes on the aggregation of platelets and tumor cells

Keil¹,

Zeisig²,

Fichtner³

2005

Thromb Haemost

View full text Add to dashboard Cite

show abstract

Untitled

Гаенко

Козлов

Сапрыкина

et al. 2002

Bulletin of Experimental Biology and Medicine

View full text Add to dashboard Cite

We studied adhesive properties and physiological activity in vivo of cells from Lewis lung carcinoma and its metastases. These cells differed in tumorogenic activity and metastatic potential in the syngeneic system. In vivo non-metastasizing cells are characterized by a lower content of surface lectins to tetrasaccharides SiaLex [Neu5Aca2-3Galb1-4(Fuca1-3) GlcNAcb] and SiaLea [Neu5Aca2-3Galb1-3(Fuca1-4)GlcNAcb] and trisaccharide HSO3Lex [HSO32-3Galb1-4(Fuca1-3)GlcNAcb] compared to cells forming metastases in the syngeneic system. Metastatic cells with low tumorogenic activity weakly expressed lectins to disaccharide ligands 6-SiaLac [Neu5Aca2-6Galb1-4Glc], 6-HSO3LacNAc, and A-di [GalNAca 1-3Galb] and trisaccharides H-type 1 [Fuca1-2Galb1-3GlcNAc and Lex [Fuca1-3(Galb 1-4)GlcNAc] compared to cells that initiated tumor formation in the syngeneic system (similarly to transplanted tumors). We hypothesized that cell receptors to these carbohydrate determinates are involved in the development and growth of primary tumors, while lectins to SiaLex, SiaLea, and HSO3Lex play a role in the progress of tumor process and metastasizing.

show abstract

The Synthesis of Photoaffinity Neoglycolipid Probes as Tools for Studying Membrane Lectins

Водовозова

Pazynina

Tuzikov

et al. 2004

Russian Journal of Bioorganic Chemistry

View full text Add to dashboard Cite

A method for the synthesis of photoaffinity neoglycolipid probes with a highly efficient carbene-generating diazocyclopentadien-2-ylcarbonyl (Dcp) label, which can be radioiodinated under standard oxidation conditions, was developed. The probes are intended for incorporation into the lipid bilayer. They are lipophilic glycoconjugates on the basis of an amphiphilic aglycone built up from a diacylglycerol and a polyethylene glycol spacer (with a polymerization degree of 9-16) bearing the Dcp label at the terminal unit. The location of the label in the aglycone provides the possibility of one-step preparation of a wide range of probes using various carbohydrate synthons. We have synthesized photoaffinity neoglycoconjugates containing the oligosaccharides: sialyl LewisX tetrasaccharide and A trisaccharide, which is specific to some tumor cells. A probe containing an inactive pentaol (aminodeoxyglucitol) was also synthesized to detect nonspecific binding. The Dcp label is bound to the probe molecule by ester bond; its lability under alkaline conditions facilitates the analysis of cross-linked products after photoaffinity labeling. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also http://www.maik.ru.

show abstract

Saccharide‐assisted delivery of cytotoxic liposomes to human malignant cells

Cited by 3 publications

References 19 publications

Effect of surface modified liposomes on the aggregation of platelets and tumor cells

Effect of surface modified liposomes on the aggregation of platelets and tumor cells

Untitled

The Synthesis of Photoaffinity Neoglycolipid Probes as Tools for Studying Membrane Lectins

Contact Info

Product

Resources

About