Targeted photodestruction of human colon cancer cells using charged 17.1A chlorine6 immunoconjugates

Abstract

The goal of this study was to develop a strategy for the selective destruction of colorectal cancer cells. Towards this end, photoimmunoconjugates were prepared between the anti-colon cancer monoclonal antibody 17.1A and the photosensitizer (PS) chlorine6(ce6). Polylysine linkers bearing several ce6molecules were covalently attached in a site-specific manner to partially reduced IgG molecules, which allowed photoimmunoconjugates to bear either cationic or anionic charges. The conjugates retained immunoreactivity as shown by enzyme-linked immunosorbent assays and by competition studies with native antibody. The overall charge on the photoimmunoconjugate was an important determinant of PS delivery. The cationic photoimmunoconjugate delivered 4 times more ce6to the cells than the anionic photoimmunoconjugate, and both 17.1A conjugates showed, in comparison to non-specific rabbit IgG conjugates, selectivity for antigen-positive target cells. Illumination with only 3 J cm−2of 666 nm light reduced the number of colony forming cells by more than 90% for the cationic 17.1A conjugate and by 73% for the anionic 17.1A conjugate after incubation with 1 μM ce6equivalent of the respective conjugates. By contrast, 1 μM free ce6gave only a 35% reduction in colonies. These data suggest photoimmunoconjugates may have applications in photoimmunotherapy where destruction of colorectal cancer cells is required. © 2000 Cancer Research Campaign

Characterization of a Conjugate between Rose Bengal and Chitosan for Targeted Antibiofilm and Tissue Stabilization Effects as a Potential Treatment of Infected Dentin

“…The rate of singlet production by CSRB was higher than and biphasic compared to that of RB. Increases in the uptake of photosensitizers by colorectal cancer cells following conjugation with cationic molecules have been reported in the past (11). Similarly, CSRB particles synthesized were cationic and were therefore taken up into the cytoplasm of the fibroblasts in contrast to RB, which is anionic.…”

Delivery of ribosome-inactivating protein toxin into cancer cells with shock waves

“…Resuspended washed cells were plated in 35-mm culture dishes incubated for 10-14 days with medium changes every other day. The number of colonies larger than 50 cells were counted using an inverted microscope [10] and survival fractions were calculated from controls as described above.…”

Preparation of chlorin e6–monoclonal antibody conjugate and its effect for photodynamic therapy

“…Therefore, compounds with higher selective affinity for tumors, more adequate for PDT, have been developed. Increased binding affinity for tumors has been obtained by conjugating the photosensitizer with monoclonal antibodies that recognize tumor-associated antigens [3][4][5][6]. These photosensitizer-immunoconjugates can deliver photosensitizers to tumors as long as the antibody maintains its binding affinity for the tumor.…”