Liposomes in cancer therapy

Daoud, Sayed S.; Hume, Lisbeth R.; Juliano, R. L.

doi:10.1016/0169-409x(89)90029-x

Cited by 21 publications

(14 citation statements)

References 43 publications

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“…During the last several years, attention has focused on the use of synthetic phospholipid vesicles (liposomes) to deliver drugs to various organ sites in vivo [129][130][131][132][133][134][135][136]. During the last several years, attention has focused on the use of synthetic phospholipid vesicles (liposomes) to deliver drugs to various organ sites in vivo [129][130][131][132][133][134][135][136].…”

Section: Systemic Activation Of Macrophages By Liposomes Containing Imentioning

confidence: 99%

“…First, the liposomes must readily bind to and be phagocytosed by free and fixed phagocytes; second, they must retain the encapsulated agent for an adequate length of time; third, they must localize to macrophages in organs where metastases occur; and fourth, they must prevent degradation of the entrapped drug [135]. First, the liposomes must readily bind to and be phagocytosed by free and fixed phagocytes; second, they must retain the encapsulated agent for an adequate length of time; third, they must localize to macrophages in organs where metastases occur; and fourth, they must prevent degradation of the entrapped drug [135].…”

Section: The Interaction Of Macrophages With Liposomesmentioning

confidence: 99%

“…The distribution of intravenously administered liposomes is determined by their physical size, composition, charge, and size of the inoculum (Tables 1 and 2) [135,145]. Although distribution patterns can be modified by manipulating these parameters, the majority of infused liposomes are taken up by cells of the RES, principally those of the liver and spleen [135,135].…”

Section: The Interaction Of Macrophages With Liposomesmentioning

confidence: 99%

“…Passage of small liposomes into visceral tissues does not occur in organs that contain continuous capillaries (lungs) [144]. In addition, circulating phagocytes are also capable of engulfing liposomes within the vascular compartment [135,144,145]. Thus, liposomes are removed from the circulation mainly by fixed or free phagocytic cells, and not by extravasation.…”

Section: The Interaction Of Macrophages With Liposomesmentioning

confidence: 99%

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Macrophages and cancer

et al. 1990

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The uncontrolled growth of metastases resistant to conventional therapeutic modalities is a major cause of death from cancer. Data from our laboratory and others indicate that metastases arise from the nonrandom spread of specialized malignant cells that preexist within a primary neoplasm. These metastases can be clonal in their origin, and different metastases can originate from different progenitor cells. In addition, metastatic cells can exhibit an increased rate of spontaneous mutation compared with benign nonmetastatic cells. These data provide an explanation for the clinical observation that multiple metastases can exhibit different sensitivities to the same therapeutic modalities. These findings suggest that the successful therapy of disseminated metastases will have to circumvent the problems of neoplastic heterogeneity and the development of resistance. Appropriately activated macrophages can fulfill these demanding criteria. Macrophages can be activated to become tumoricidal by interaction with phospholipid vesicles (liposomes) containing immunomodulators. Tumoricidal macrophages can recognize and destroy neoplastic cells in vitro and in vivo, leaving nonneoplastic cells uninjured. Although the exact mechanism(s) by which macrophages discriminate between tumorigenic and normal cells is unknown, it is independent of tumor cell characteristics such as immunogenicity, metastatic potential, and sensitivity to cytotoxic drugs. Moreover, macrophage destruction of tumor cells apparently is not associated with the development of tumor cell resistance. Macrophages are found in association with malignant tumors in a definable pattern, suggesting that the most direct way to achieve macrophage-mediated tumor regression is in situ macrophage activation. Intravenously administered liposomes are cleared from the circulation by phagocytic cells, including macrophages, so when liposomes containing immunomodulators are endocytosed, cytotoxic macrophages are generated in situ. The administration of such liposomes in certain protocols has been shown to bring about eradication of cancer metastases. Macrophage destruction of metastases in vivo is significant, provided that the total tumor burden at the start of treatment is minimal. For this reason, we have been investigating various methods to achieve maximal cytoreduction in metastases by modalities such as chemotherapy or radiotherapy prior to macrophage-directed therapy. It is important to note that even the destruction of 99.9% of cells in a metastasis measuring 1 cm2 would leave 10(6) cells to proliferate and kill the host. The ability of tumoricidal macrophages to distinguish neoplastic from bystander nonneoplastic cells presents an attractive possibility for treatment of the few tumor cells which escape destruction by conventional treatments. Macrophage-directed therapy has been studied in several human protocols, yielding important biological information about the use of liposome-encapsulated macrophage activators in cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Systemic Activation Of Macrophages By Liposomes Containing Imentioning

confidence: 99%

Section: The Interaction Of Macrophages With Liposomesmentioning

confidence: 99%

Section: The Interaction Of Macrophages With Liposomesmentioning

confidence: 99%

Section: The Interaction Of Macrophages With Liposomesmentioning

confidence: 99%

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Macrophages and cancer

et al. 1990

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“…In parallel experiments, rhTNF at 0.001, 0.01, 0.1, l, and 10 ng/ml produced 6%, 21%, 52%, 88%, and 95% lysis, respectively, of L-929 cells Liposomes provide a unique carrier vehicle for the delivery of biologically active materials to phagocytic cells in vivo. Like any other circulating particle, liposomes are rapidly cleared by fixed and free phagocytic cells [3,6,11,12,50,55]. We have taken advantage of this natural physiological fate of liposomes to deliver immunomodulators to cells that belong to the reticuloendothelial system.…”

Section: Activation Of Tumoricidal Properties In Mouse Macrophgesmentioning

confidence: 99%

Comparative efficacy of liposomes containing synthetic bacterial cell wall analogues for tumoricidal activation of monocytes and macrophages

Utsugi

Nii

Fan

et al. 1991

Cancer Immunol Immunother

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We examined the activation to the tumoricidal state of normal mouse peritoneal exudate macrophages, bone marrow macrophages, and human blood monocytes by liposomes containing either lipophilic muramyl tripeptide (CGP 19,835) or a new synthetic analogue of lipoprotein from gram-negative bacteria outer wall, CGP 31,362, or combinations of the two. The superiority of liposomes containing the synthetic lipopeptide over liposomes containing lipophilic muramyl tripeptide for in vitro activation of monocytes and macrophages was demonstrated in several experiments. First, liposome-CGP-19,835 activated monocytes only in the presence of interferon-gamma, whereas activation with liposome-CGP 31,362 was interferon-independent. Second, activation of both mouse macrophages and human blood monocytes by liposome-CGP 31,362 occurred at a lower liposomal concentration than that by liposome-CGP 19,835. Third, monocytes incubated with liposome-CGP 31,362 released both tumor necrosis factor (TNF) and interleukin-1 activities, whereas monocytes treated with liposome-CGP 19,835 (in the absence of interferon-gamma) released only TNF activity. These data suggest that liposomes containing the synthetic lipopeptide CGP 31,362 are superior to liposomes containing CGP 19,835 for systemic activation of macrophages.

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