Enhancement of growth of a radiation-induced lymphoma by T cells from normal mice

Gabizón, Alberto; Trainin, Nathan

doi:10.1038/bjc.1980.279

Cited by 11 publications

(7 citation statements)

References 27 publications

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“…into the hind leg with 106 tumor cells of the J6456 lymphoma (33). Mice were tested 2-3 weeks after tumor inoculation when the local tumor implants weighed between 0.5 and 2 g. The liver weights were within the normal range, although microscopic dissemination of the tumor to the liver is often present at this advanced stage (33). Phospholipid dose, route of injection, and other details of the biodistribution analysis were as for normal mice.…”

Section: Methodsmentioning

confidence: 99%

Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors.

Gabizón

Papahadjopoulos

1988

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

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The rapid clearance of circulating liposomes from the bloodstream, coupled with their high uptake by liver and spleen, has thus far been an obstacle to any attempts at targeting to tumors. We have assessed the impact of liposome composition on their clearance from the circulation in normal and tumor-bearing mice and on their uptake by tumors and various normal tissues. By selective changes in lipid composition, while maintaining a mean particle diameter of '100 nm, we have achieved up to a 60-fold increase in the fraction of recovered dose present in blood 24 hr after i.v. i 'ection. Concomitantly, there was a decrease by a factor of 4 of the recovered dose localizing in the liver and spleen, the major organs of the reticuloendothelial system. Parallel experiments in tumor-bearing mice demonstrated a 25-fold increase of the liposome concentration in the tumor when formulations with long and short blood residence time were compared. The most favorable results were obtained with liposomes containing a small molar fraction of a negatively charged glycolipid, such as monosialoganglioside or phosphatidylinositol, and a solidphase neutral phospholipid as the bulk component. The biodistribution of such formulations is of considerable therapeutic potential in cancer for increasing the concentration of cytotoxic agents in tumors while minimizLing the likelihood of toxicity to the reticuloendothelial system. Liposome encapsulation has been proven useful for reducing the toxicity of certain drugs (1-6) as well as for enhancing the efficacy of macrophage-activating factors (7,8) and drugs directed against parasites residing within the reticuloendothelial system (RES) (9)(10)(11)(12). The propensity of the RES to remove liposomes from the circulation has thus far limited the prospect oftargeting liposomes to tissues other than liver, spleen, and lung (13-15).Designing liposomes with prolonged circulation time would require a reduction of the rate of their clearance by the RES and of the leakage of liposome contents in the bloodstream. Our strategy to achieve these goals was based on the following prior observations. (i) The inclusion of cholesterol (Chol) and solid-phase phospholipids such as sphingomyelin and distearoyl phosphatidylcholine has been shown to increase liposome stability in plasma as determined by the degree of retention of various liposome-encapsulated markers in vitro (16-18). (ii) The same solid-phase phospholipids (sphingomyelin or distearoyl phosphatidylcholine) in the form of small sonicated liposomes are cleared more slowly after intravenous injection than those made with fluid phospholipids such as egg yolk phosphatidylcholine (PtdCho) (19)(20)(21)(22). (iii) The inclusion of certain gangliosides, which confer to the liposome surface a negative charge and increased hydrophilicity, synergizes with Chol to enhance liposome stability in plasma (23) and prolongs liposome half-life in blood with a concomitant decrease in liver and spleen uptake (24). In addition, inclusion of phosphatidylinositol (P...

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Section: Methodsmentioning

confidence: 99%

Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors.

Gabizón

Papahadjopoulos

1988

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

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488

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“…Tumour cells were obtained from a BALB/c, radiation-induced, T-cell derived lymphoma (J-6456) described previously (Gabizon & Trainin, 1980 (Gabizon et al, 1982). Briefly, 50-65% of the initial amount of ADM was retained in the liposomes using a 3:7 molar ratio of either phosphatidylserine (PS): phosphatidylcholine (PC) or phosphatidylglycerol (PG): PC, respectively.…”

Section: Methodsmentioning

confidence: 99%

Superior therapeutic activity of liposome-associated adriamycin in a murine metastatic tumour model

Gabizón¹,

Goren²,

Fuks³

et al. 1985

Br J Cancer

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The use of liposomes as carriers of adriamycin (ADM) seems to offer important advantages with regard to the attenuation of the dose-dependent anthracycline-induced cardiomyopathy. This effect has been shown in rodents (Rahman et al., 1980(Rahman et al., , 1982Forssen & Tokes, 1981;Olson et al., 1982) and dogs (Herman et al., 1983) and is apparently related at least partially to the reduced uptake of the drug in the cardiac tissue of animals treated with liposome-entrapped ADM (L-ADM) (Forssen & Tokes, 1979, 1983 Rahman et al., 1980;Gabizon et al., 1982Gabizon et al., , 1983Olson et al., 1982). Obviously, if this delivery system is to be useful therapeutically, it is crucial to evaluate its anti-tumour activity. Since liposomes home preferentially in tissues with sinusoidal capillaries and rich in cells of the reticuloendothelial system, such as the liver and spleen (Segal et al., 1974;Poste et al., 1982), it is reasonable to assume that tumour colonies residing in these organs constitute a suitable target for liposome-mediated delivery of cytotoxic drugs. The purpose of this paper is to describe the antitumour In previous studies we showed that liposomes containing negatively charged phospholipids capture ADM very efficiently and cause important changes in the tissue distribution of the drug, viz. decreased levels in the heart and increased and sustained levels in the liver and spleen. These changes were observed in normal (Gabizon et al., 1982) and in tumour-bearing mice (Gabizon et al., 1983). Furthermore, when metastatic tumour cells were isolated from the liver we found significantly higher intracellular levels of ADM in tumour cells of mice treated with L-ADM as compared to free ADM treatment. Also, the proliferative ability of intrahepatic metastatic cells in in vitro qultures and in vivo transfer assays was markedly more impaired after L-ADM treatment than after ADM alone (Gabizon et al., 1983).These results, and especially the ability of liposomes to increase the intracellular levels of ADM in liver-residing tumour cells, provided a rational basis for therapeutic experiments. In the present study, we have compared the survival of tumour-inoculated mice treated either with L-ADM or with free ADM using the metastatic liver model of the J-6456 lymphoma. Our results suggest that the therapeutic index of ADM can be significantly improved by liposome association in a group of

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“…[50][51][52][53] However, the cardiotoxicity of the free drug limits dosage. [50,51] Liposomes have been developed as Dox delivery carriers and can certainly reduce the accumulation of the drug in the heart; therefore, polymersome encapsulation of Dox might be expected to reduce leakage and also to provide novel release mechanisms compared to liposomes. [50] Dox was entrapped in the OPA 215 vesicles by a standard method of encapsulation with an acid gradient across the membrane.…”

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confidence: 99%

Temperature‐Controlled Assembly and Release from Polymer Vesicles of Poly(ethylene oxide)‐block‐ poly(N‐isopropylacrylamide)

et al. 2006

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Narrow‐dispersity thermoresponsive block copolymers of poly(ethylene oxide)‐block‐poly(N‐isopropylacrylamide) self‐assemble into vesicles at temperatures above 32 °C. The vesicles integrate a hydrophobic fluorescent dye into their membranes and encapsulate the hydrophilic anticancer drug doxorubicin. Temperature‐controlled release of the dye through disintegration of the vesicles takes place at temperatures below 32 °C, as shown in the figure.

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Enhancement of growth of a radiation-induced lymphoma by T cells from normal mice

Cited by 11 publications

References 27 publications

Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors.

Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors.

Superior therapeutic activity of liposome-associated adriamycin in a murine metastatic tumour model

Temperature‐Controlled Assembly and Release from Polymer Vesicles of Poly(ethylene oxide)‐block‐ poly(N‐isopropylacrylamide)

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