Tumor liposomes

Yoshida J, Mizuno M. Clinical gene therapy for brain tumors. Liposomal delivery of anticancer molecule to glioma. J Neurooncol 2003 65(3) 261-267. 

Liposomal encapsulation of DOX or DNR Preferred anthracycline delivery to the tumor Breast cancer, ovarian cancer, AIDS-related Kaposi s sarcoma, multiple myeloma (pegylated liposomal DOX). Breast cancer (uncoated liposomal DOX). AIDS-related Kaposi s sarcoma, acute mye-loblastic leukemia, multiple myeloma, non-Hodgkin s lymphomas (uncoated liposomal DNR)... 

DOX, as EPI seems to form fewer amounts of ROS and secondary alcohol metabolite, (ii) encapsulation of anthracyclines in uncoated or pegylated liposomes that ensure a good drug delivery to the tumor but not to the heart, (iii) conjugation of anthracyclines with chemical moieties that are selectively recognized by the tumor cells, (iv) coadministration of dexrazoxane, an iron chelator that diminishes the disturbances of iron metabolism and free radical formation in the heart, and (v) administration of anthracyclines by slow infusion rather than 5-10 min bolus (Table 1). Pharmacological interventions with antioxidants have also been considered, but the available clinical studies do not attest to an efficacy of this strategy. 

Nanotechnology has led to very efficient versions of liposomes. Tiny hollow spheres only nanometers in diameter hold even tinier capsules of medicine. The spheres are made of silica covered with gold nanoparticles and when they are coated with antibodies they attach to tumor cells. The spheres are sensitive to light of specific wavelengths and when the light is applied, either heat up and destroy the tumor, or burst, releasing the drugs within the capsules directly into the tumor. 

Increased accumulation of liposomes, especially small liposomes, has been reported to occur at sites of inflammation (Williams et al., 1986) and in tumors (Turner et al., 1988 Gabizon and Papahadjopoulos, 1988) (cf. Sec. VI.B). However, it is well established that endo-cytosis of liposomes by MPS cells, primarily those located in liver and spleen, accounts for most of the uptake of liposomes—and, in general, uptake of particulate matter—from the blood circulation. 

FIGURE 9 Antitumor activity of liposome-encapsulated cDDP and free cDDP in solid IgM immunocytoma-bearing Lou/M rats. Tumorbearing rats were injected with 2 mg cDDP/kg body weight twice a week (arrow). Tumor diameter at the start of the experiment was 2-3 cm. Tumor growth during treatment is presented (mean SD of six animals unless otherwise indicated). Liposomes DPPC/DPPG/ chol (molar ratio 10 1 10) size about 0.7 pm. PC/PS/chol (molar... 

Begent, R. H. J., Green, A. J., Bagshawe, K. D., Jones, B. E., Keep, P. A., Searle, F., Jewkes, R. F., Barrat, G. M., and Ryman, B. E. (1982). Liposomally entrapped second antibody improves tumor imaging with radiolabelled (first) antitumor anti-body. Lancet, 2, 739-742. 

Gabizon, A., and Papahadjopoulos, D. (1988). Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors, Proc. Natl. Acad. Sci. USA, 85, 6949-6953. 

Hashimoto, Y., Sugawara, M., Masuko, T., and Hojo, H. (1983). Antitumor effect of actinomycin D entrapped in liposomes bearing subunits of tumor-specific monoclonal immunoglobulin M antibody. Cancer Res., 43, 5328-5334. 

D. (1978). Effect of lipid vesicle (liposome) encapsulation of methotrexate on its chemotherapeutic efficacy in solid rodent tumors. Cancer Res., 38, 2848-2853. 

Mayhew, E., and Rustum, Y. (1983). Effect of liposome entrapped chemotherapeutic agents on mouse primary and metastatic tumors, Biol. Cell. 81-85. 

Uliana, J. A., Gamble, R. C., and Baldeschwieler, J. D. (1983). Liposomal blockade of the reticuloendothelial system Improved tumor imaging with small unilamellar vesicles. Science. 220. 502-505. 

Schroit, A. J., and Key, M. E. (1983). Induction of syngeneic tumor-specific immunity by liposomes reconstituted with L2C tumor-cell antigens, Immunology. 49. 431-438. 

Storm, G., Roerdink, F. H., Steerenberg, P. A., De jong, W. H., and Crommelin, D. J. A. (1987). Influence of lipid composition on the antitumor activity exerted by doxorubicin-containing liposomes in a rat solid tumor model, Cancer Res., 47, 3366-3372. 

M. (1987). Tumor targeting potential of liposomes encapsulating Ga-67 and antibody to Dalton s lymphoma associated antigen (anti-DLAA), Int. J. Rad. Oncol. Biol. Phys.. 13, 1713-1719. 

Yatvin, M. B., Miihlensiepen, H., Porschen, W., Weinstein, J. N., and Feinendegen, L. E. (1981). Selective delivery of liposome-associated cis-dichlorodiammineplatinum(II) by heat and its influence on tumor drug uptake and growth. Cancer Res.. 41. 1602-1607. 

When liposomes are formed, they can be made to entrap certain compounds inside themselves, eg, drugs and isolated genes. There is interest in using liposomes to distribute drugs to certain tissues, and if components (eg, antibodies to certain cell surface molecules) could be incorporated into liposomes so that they would be targeted to specific tissues or tumors, the therapeutic impact would be considerable. DNA entrapped inside liposomes appears to be less sensitive to... 

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