Fate of Protein‐Containing Liposomes Injected into Rats

Gregoriadis, Gregory; Ryman, Brenda E.

doi:10.1111/j.1432-1033.1972.tb19710.x

Cited by 317 publications

(97 citation statements)

References 16 publications

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“…However, liposomes injected i.v. are mainly taken up by the cells of the liver and spleen (Gregoriadis & Ryman, 1972). Specific accumulation of liposomes in tumours, and particularly in tumour cells, would be of considerable advantage in improving the selectivity of anti-cancer drugs.…”

mentioning

confidence: 99%

Tissue distribution and tumour localization of 99m-technetium-labelled liposomes in cancer patients

Richardson¹,

Ryman²,

Jewkes³

et al. 1979

Br J Cancer

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The possible use of liposomes (phospholipid vesicles) to direct cytotoxic drugs to tumours has led us to investigate the tissue localization of i.v. injected 99m-Tc-labelled liposomes in cancer patients. Twenty mg or 300 mg doses of liposomal lipid (7:2:1 molar ratio of phosphatidylcholine : cholesterol : phosphatidic acid) were used in a study of 13 patients with advanced cancer and one with polycythaemia rubra vera (PRV). In all cases except the patient with PRV the major site of uptake of the label was the liver and spleen. In the patient with PRV the liver uptake was greatly reduced and the major site of uptake was found in regions corresponding to marrow. With the exception of one patient with a primary hepatoma, there was no significant tumour uptake of the label. Images Fig. 2 Fig. 3

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confidence: 99%

Tissue distribution and tumour localization of 99m-technetium-labelled liposomes in cancer patients

Richardson¹,

Ryman²,

Jewkes³

et al. 1979

Br J Cancer

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“…Unfortunately, when liposomes encounter the membranes of cells or organelles, they tend to resist uptake (6), provoke fusion with cell membranes (7,8), or remain adsorbed to cell surfaces where their contents remain unavailable to the cell interior (6). Although studies in vivo have shown uptake by rat liver and spleen of enzymes originally associated with injected liposomes (9,10), no compelling evidence has been presented that enzymes captured by liposomes can be endocytosed by lysosomes of undamaged cells in the absence of surface adsorption or direct fusion.…”

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confidence: 99%

A general method for the introduction of enzymes, by means of immunoglobulin-coated liposomes, into lysosomes of deficient cells.

Weissmann¹,

Bloomgarden²,

Kaplan³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

163

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Phagocytes of the smooth dogfish (Mustelus canis) contain no endogenous peroxidase within their lysosomes and constitute models for cells genetically deficient in lysosomal enzymes such as myeloperoxidase. We have obtained uptake of over 50% of exogenous horseradish peroxidase, provided the enzyme is exhibited to cells after incorporation into liposomes coated with heat-aggregated (620, 10 min), isologous IgM. Trapping of horseradish peroxidase (EC 1.11.1.7) by liposomes was established by chromatographic resolution (Sephadex G-200; Sepharose 2B and 4B) of free enzyme from that associated with liposomes; liposome-associated horseradish peroxidase, together with trapped markers of the aqueous compartment (glucose, CrO4=), were excluded, and free enzyme and markers were retained. Enzyme and marker trapping was not electrostatic, varied with the molar ratio of charged membrane components, and was reversed by detergent lysis (Triton X-100) of liposomes. Uptake at 300 of aggregated IgM-coated liposomes containing trapped horseradish peroxidase exceeded that of free enzyme by 100-fold, and was more efficient than uptake of horseradish peroxidase presented in uncoated liposomes or in liposomes coated with native IgM. After phagocytosis, peroxidaserich liposomes were localized exclusively in lysosomes of the phagocytes by ultrastructural histochemistry; the enzyme displayed over 50% latency to osmotic lysis. This method may prove to be of general use in the provision of exogenous enzymes to phagocytic cells genetically deficient in lysosomal hydrolases.

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“…When uptake was expressed as activity in whole organ, the liver became the most effective one (Fig. 1b), as observed by others (Gregoriadis and Ryman 1972). Relatively high et al…”

Section: Blood Content Of Brainmentioning

confidence: 49%