Specific Hybrid Liposomes Composed of Phosphatidylcholine and Polyoxyethylenealkyl Ether with Markedly Enhanced Inhibitory Effects on the Growth of Tumor Cells In Vitro.

Matsumoto, Yōko; Imamura, Chikara; Ito, Takatoshi; Taniguchi, Chiho; Ueoka, Ryuichi

doi:10.1248/bpb.18.1456

Cited by 33 publications

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“…In the reaction field of hybrid liposomes, composed of vesicular and micellar molecules including the active tripeptide, high or perfect enantioselective catalysis for the discrimination of the L-form substrate from the D-form was attained by changing the ionic strength, the species of molecules and the composition of liposomes. 6 Hybrid liposomes are effective for inhibiting the growth of various tumor cells in vitro [7][8][9] and in vivo using an animal model of carcinoma, 10,11 as well as their application for drug delivery. 12 In addition, hybrid liposomes have proven to be a safe material by experiments with normal animals and are being employed in a clinical study.…”

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confidence: 99%

Novel mechanism of hybrid liposomes‐induced apoptosis in human tumor cells

Matsumoto

Iwamoto

Matsushita

et al. 2005

Intl Journal of Cancer

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Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of these liposomes, such as size, membrane fluidity, phase transition temperature and hydrophobicity can be controlled by changing the composition. Hybrid liposomes composed of dimyristoylphosphatidylcholine and polyoxyethylene (10) dodecyl ether were found to inhibit the growth of human promyelocytic leukemia (HL-60) cells without using any drugs. Induction of apoptosis by hybrid liposomes in HL-60 cells was verified on the basis of fluorescence microscopy and flow cytometry analysis, after fusion and accumulation of hybrid liposomes, which was revealed on the basis of microphysiometer. We elucidated the pathways of apoptosis induced by the hybrid liposomes. That is, hybrid liposomes fused and accumulated in tumor cell membranes, and the apoptosis signal first passed through mitochondria, caspase-9 and caspase-3, second through Fas, caspase-8, caspase-3 and then reached the nucleus. Hybrid liposomes themselves can induce apoptosis in human tumor cells along with high inhibitory effects on the growth of tumor cells. ' 2005 Wiley-Liss, Inc.

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Novel mechanism of hybrid liposomes‐induced apoptosis in human tumor cells

Matsumoto

Iwamoto

Matsushita

et al. 2005

Intl Journal of Cancer

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“…In this study, we loaded liposomes bearing active saccharide vector (HSO3Le x or HSO3Le a conjugates), or inactive one (GlcNAcfl conjugate) with DG-sarcolysine and examined cytotoxic properties of such Sug-liposomes in comparison with that of loaded liposomes without any vector, liposomes themselves, and unmodified sarcolysine. A weak cytotoxic effect of empty liposomes can be related to some antineoplastic properties reported for liposomal preparations with no specific antitumor agent [25]. The inclusion of GlcNAcfl conjugate at the surface of drug-loaded liposomes did not alter significantly their toxicity for tumor cells.…”

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confidence: 83%

Saccharide‐assisted delivery of cytotoxic liposomes to human malignant cells

et al. 1998

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SUMMARY: The overexpression of lectins by malignant cells was applied for in vitro targeting of liposomes equipped with a saccharide vector and loaded in the lipid phase with a lipid derivative of anticancer agent sarcolysine. The lectin specificity of human leukemia HL-60 and human lung adenocarcinoma ACL cells was revealed by tests with fluorescein-labeled sugar probes. With the help &fluorescent lipid dye it was shown that active saccharide ligands increased the level of the vectored liposome binding to malignant cells by 50-80% as compared to liposomes without vector or with inactive one. The degree of liposome/cell membrane fusion was monitored fluorometrically and was shown to be complete and independent of the vectors. The targeted drugloaded liposomes had the cytotoxic activity 2-4 times higher as compared to the vector-free ones.

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“…14,15) In this study, we report on the remarkable effects (composition of hybrid membranes and reaction temperature) on the enantioselective hydrolysis of C 12 -D(L)-Phe-PNP catalyzed by Z-PheHisLeu in the hybrid membranes composed of phospholipid (DMPC) and nonionic surfactant (C 12 (EO) 8 ) at pH 7.4. The relations between the enantioselectivity and the microenvironment of the reaction fields are discussed.…”

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confidence: 99%

Steric-Control for the Enantioselective Hydrolysis of Amino Acid Esters in Hybrid Membrane Systems.

Tanoue

Ichihara

Goto

et al. 2003

CHEMICAL & PHARMACEUTICAL BULLETIN

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Stereoselective reactions have attracted considerable attention in connection with understanding the origins of the stereoselectivity observed with proteolytic enzymes. [1][2][3][4][5] In the course of our study on the stereoselective hydrolysis (deacylation) of amino acid and dipeptide esters with the functional molecular assemblies composed of synthetic surfactants and reactive species, we emphasized that the stereochemical (enantiomeric and diastereomeric substrates) control could be attained by changing the composition of the coaggregates [6][7][8] and regulating ionic strength 9) and temperature.10,11) Especially, an extremely high enantioselectivity was attained at the optimum composition of coaggregate. 6)However, the values of k t and k s (the first-order rate constants with and without the peptide catalyst, respectively) are fairly close for the enantioselective hydrolysis in the aggregate systems of synthetic surfactants. Then, it is impossible to disregard the errors of k t and k s values when we discuss catalytic activities of the artificial membranes bound enzyme on the basis of k a,obsd values.In this study, we employed native phospholipids instead of synthetic surfactants for the hydrolysis of amino acid esters12) with tripeptide (Z-PheHisLeu) 12) in the coaggregate systems. The advantage of this experiment should enable to evaluate of the catalytic activities directly on the basis of k a,obsd values because of the large difference of the k t and k s values, that is, the k t /k s ratios were above 30 and 4 folds for the L-and D-substrates, respectively.Recently, in the course of our study on artificial membranes composed of native phospholipids, very useful knowledges for medical engineering applications in vitro and in vivo have been obtained. For example, artificial lipid membranes were used as a drug carrier in drug delivery systems, such as 1,3-bis(2-chloroethyl)-1-nitrosourea encapsulated in hybrid liposomes (artificial membranes) which should be effective against malignant glioma in vitro and in vivo. 13)Moreover, the artificial membranes themselves were found to be useful as a new type of anticancer drug without side effects. 14,15) In this study, we report on the remarkable effects (composition of hybrid membranes and reaction temperature) on the enantioselective hydrolysis of C 12 -D(L)-Phe-PNP catalyzed by Z-PheHisLeu in the hybrid membranes composed of phospholipid (DMPC) and nonionic surfactant (C 12 (EO) 8 ) at pH 7.4. The relations between the enantioselectivity and the microenvironment of the reaction fields are discussed. Results and DiscussionThe composition dependence of coaggregates on the enantioselective hydrolysis of C 12 -D(L)-Phe-PNP catalyzed by Z-PheHisLeu was investigated in hybrid membranes of DMPC/C 12 (EO) 8 , as shown in Fig. 1. The concentration of C 12 (EO) 8 is expressed as mol% of total lipids. Both the second-order rate constants (k a,obsd ) and enantioselectivity (k ; 4-22-1 Ikeda, Kumamoto 860-0082, Japan. Received November 5, 2002; accepted November 26, 20...

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Specific Hybrid Liposomes Composed of Phosphatidylcholine and Polyoxyethylenealkyl Ether with Markedly Enhanced Inhibitory Effects on the Growth of Tumor Cells In Vitro.

Cited by 33 publications

References 0 publications

Novel mechanism of hybrid liposomes‐induced apoptosis in human tumor cells

Novel mechanism of hybrid liposomes‐induced apoptosis in human tumor cells

Saccharide‐assisted delivery of cytotoxic liposomes to human malignant cells

Steric-Control for the Enantioselective Hydrolysis of Amino Acid Esters in Hybrid Membrane Systems.

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