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• W1979995732 abstract "Chlorin e6 and HPMA copolymer-bound chlorin e6 were compared with chlorin e6 polymer conjugates containing galactosamine or anti-Thy 1.2 antibody as targeting moieties. Galactosamine recognizes asialoglycoprotein receptors on the human hepatocarcinoma cell line PLC/PRF/5 and the anti-Thy 1.2 antibody interacts with Thy 1.2 alloantigens on mouse splenic T cells. The efficiency of photodynamic injury as a function of incubation time and temperature, and irradiation time was studied. Two-day-old cultures of PLC/PRF/5 cell line were most sensitive to HPMA copolymer bound chlorin e6 (targeted or nontargeted), whereas no differences were observed when free drug was tested on 1-, 2-or 3-day-old cultures. Dark toxicity of the free drug was observed at concentrations as low as 2 × 10−6 M. Dark toxicity decreased when chlorin e6 was bound to HPMA copolymers, especially to conjugates containing targeting moieties. The effect of incubation time was seen only in the hepatocarcinoma cell culture. For galactosamine-targeted HPMA copolymer bound chlorin e6, 2–3 h were necessary to induce a pronounced killing effect. For anti-Thy 1.2 targeted polymeric drug and for free chlorin e6, 1 h of incubation was sufficient to load the cells with a photolytic dose of chlorin e6. Dependence on the time of irradiation was observed in both targeted conjugates. One hour of irradiation induced only limited photolysis, whereas 7.5 h of irradiation was necessary for substantial photodynamic injury. Photodynamic destruction of cells exposed to free drug was similar for irradiation periods of 1–7.5 h. In accordance with the mechanism of cellular uptake of polymeric conjugates by receptor-mediated endocytosis, the conjugates were less photodynamically active when incubated with cell cultures at a lower (4°C) temperature. Nontargeted polymeric chlorin e6 was always considerably less phototoxic when compared to targeted HPMA copolymer conjugates. Antibody response to thymus-dependent antigen (SRBC) induced in vitro is more sensitive to the targeted photosensitizer, if compared with the estimation of cell viability. It suggests that lower concentrations of the photosensitizer do not destroy (desintegrate) the target cells, but their function and/or proliferation may be impaired. Binding of antibodies via carbohydrate moieties in the Fc portion of the anti-Thy 1.2 molecule increases the photodestructive capacity of the antibody targeted photosensitizer, when compared to conjugates where the antibody was bound via Nε-amino groups of lysine residues. A concentration of 1 × 10− M of chlorin e6 in the former conjugate kills 40%, and a concentration of 1 × 10−8 M 30% of target T cells while the latter conjugate and free drug are ineffective at the above mentioned concentrations. The results obtained from these two in vitro models allowed us to compare the photodynamic effect of targeted HPMA copolymer bound chlorin e6 on a hepatocarcinoma cell line (model of anticancer treatment) and on normal lymphocytes (model of immunosuppression)." @default.
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• W1979995732 title "Targetable photoactivalable drugs. 3. In vitro efficacy of polymer bound chlorin e6 toward human hepatocarcinoma cell line (PLC/PRF/5) targeted with galactosamine and to mouse splenocytes targeted with anti-Thy 1.2 antibodies" @default.
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• W1979995732 doi "https://doi.org/10.1016/0168-3659(93)90096-n" @default.
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