Immunoliposome-mediated targeting of doxorubicin to human ovarian carcinoma in vitro and in vivo

Vingerhoeds, Monique H.; Steerenberg, P. A.; Hendriks, J.J.G.W.; Dekker, L.C.; Hoesel, Q.G.C.M. van; Crommelin, Daan J.A.; Storm, Gert

doi:10.1038/bjc.1996.484

Cited by 66 publications

(25 citation statements)

References 22 publications

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“…For instance, DOX targeted on an antibody was less effective than the free drug (29) as was DOX targeted in various immunoliposomes (14,30,31). Moreover, DOX targeted by attachment to an 11.8 kDa hyaluronan was less active than free DOX (32).…”

Section: Discussionmentioning

confidence: 99%

Determination and Modeling of Kinetics of Cancer Cell Killing by Doxorubicin and Doxorubicin Encapsulated in Targeted Liposomes

et al. 2004

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Various mathematical approaches have been devised to relate the cytotoxic effect of drugs in cell culture to the drug concentration added to the cell culture medium. Such approaches can satisfactorily account for drug response when the drugs are free in solution, but the approach becomes problematic when the drug is delivered in a drug delivery system, such as a liposome. To address this problem, we have developed a simple model that assumes that the cytotoxic potency of a drug is a function of the intracellular drug level in a critical compartment. Upon exposure to drug, cell death commences after a lag time, and the cell kill rate is dependent on the amount of drug in the critical intracellular compartment. The computed number of cells in culture, at any time after exposure to the drug, takes into account the cell proliferation rate, the cell kill rate, the average intracellular drug concentration, and a lag time for cell killing. We have applied this model to compare the cytotoxic effect of doxorubicin (DOX), or DOX encapsulated in a liposome that is targeted to CD44 on B16F10 melanoma cells in culture. CD44 is the surface receptor that binds to hyaluronan and is overexpressed on various cancer cells, including B16F10. We have shown previously that the drug encapsulated in hyaluronan-targeted liposomes was more potent than was the free drug. The model required the determination of the cell-associated DOX after the cells were incubated with various concentrations of the free or the encapsulated drug for 3 h, and the quantification of cell number at various times after exposure to the drug. The uptake of encapsulated drug was greater than that of the free drug, and the ratio of cell association of encapsulated: free drug was 1.3 at 0.5 g/ml and increased to 3.3 at 20 g/ml DOX. The results demonstrate that the enhanced potency of the encapsulated drug could stem from its enhanced uptake. However, in certain cases, where larger amounts of the free drug were added, such that the intracellular amounts of drug exceeded those obtained from the encapsulated drug, the numbers of viable cells were still significantly smaller for the encapsulated drug. This finding demonstrates that for given amounts of intracellular DOX, the encapsulated form was more efficient in killing B16F10 cells than the free drug. The outcome was expressed in the kinetic model as a 5-6-fold larger rate constant of cell killing potency for the encapsulated drug versus the free drug. The model provides a quantitative framework for comparing the cytotoxic effect in cultured cells when applying the drug in the free form or in a delivery system.

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Section: Discussionmentioning

confidence: 99%

Determination and Modeling of Kinetics of Cancer Cell Killing by Doxorubicin and Doxorubicin Encapsulated in Targeted Liposomes

et al. 2004

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“…Most of these liposomes have good targeting ability in vitro or in vivo, but data on their therapeutic efficacy have been either lacking or negative (9,33). Two major factors may affect the systemic therapeutic effect: first, liposomes are removed nonspecifically, primarily by the reticuloendothelial system; and second, the leakage of doxorubicin from liposomes, which are composed of phospholipid with low phase-transition temperature, increases in biological fluids and results in loss of drug targeting (33). In the present study, we used neutral and sterically stabilized liposomes, also known as PEGylated liposomes.…”

Section: Discussionmentioning

confidence: 99%

A Novel Peptide Specifically Binding to Nasopharyngeal Carcinoma For Targeted Drug Delivery

Lee

Tseng

et al. 2004

Cancer Research

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“…The signifi cantly increased anticancer activity in several animal xenograft tumor models of the immunoliposomal preparations can be attributed to the fact, that the immunoconjugates (as well as the free antibody) are internalized rapidly by the target cells by receptor-mediated endocytosis (Park et al 2001;Park et al 2002). The importance of this observation is emphasized by studies, where liposomes conjugated to the monoclonal antibody OV-TL3 were used for the treatment of ovarian carcinoma cells in an intraperitoneal animal xenograft model (Vingerhoeds et al 1996). Despite effi cient targeting of the OA3 surface receptor on the ovarian tumor cells, no superior antitumor effects could be demonstrated in vitro or in vivo as compared to non-targeted liposomal formulations.…”

Section: Vector-conjugated Liposomesmentioning

confidence: 99%

Tumor targeting using liposomal antineoplastic drugs

Huwyler¹

2008

IJN

139

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During the last years, liposomes (microparticulate phospholipid vesicles) have been used with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumor drugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vectorconjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this fi eld of research.

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Immunoliposome-mediated targeting of doxorubicin to human ovarian carcinoma in vitro and in vivo

Cited by 66 publications

References 22 publications

Determination and Modeling of Kinetics of Cancer Cell Killing by Doxorubicin and Doxorubicin Encapsulated in Targeted Liposomes

Determination and Modeling of Kinetics of Cancer Cell Killing by Doxorubicin and Doxorubicin Encapsulated in Targeted Liposomes

A Novel Peptide Specifically Binding to Nasopharyngeal Carcinoma For Targeted Drug Delivery

Tumor targeting using liposomal antineoplastic drugs

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