Combination chemotherapy and photodynamic therapy with Fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells
The biological activities of sequential combinations of anticancer drugs, SOS thiophene (SOS) and mesochlorin e6 monoethylenediamine (Mce6), in the form of free drugs, nontargeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer - drug conjugates, P-GFLG-Mce6 and P-GFLG-SOS (P is the HPMA copolyme...
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th-mahidol.188652018-07-12T09:50:21Z Combination chemotherapy and photodynamic therapy with Fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells Jarunee Hongrapipat Pavla Kopečková Jihua Liu Sompol Prakongpan Jindřich Kopeček University of Utah Mahidol University Biochemistry, Genetics and Molecular Biology Pharmacology, Toxicology and Pharmaceutics The biological activities of sequential combinations of anticancer drugs, SOS thiophene (SOS) and mesochlorin e6 monoethylenediamine (Mce6), in the form of free drugs, nontargeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer - drug conjugates, P-GFLG-Mce6 and P-GFLG-SOS (P is the HPMA copolymer backbone and GFLG is the glycylphenylalanylleucylglycine spacer), and Fab′-targeted HPMA copolymer - drug conjugates, P-(GFLG-Mce6)-Fab′ and P-(GFLG-SOS)-Fab′ (Fab′ from OV-TL 16 antibodies complementary to CD47), were evaluated against human ovarian carcinoma OVCAR-3 cells. Mce6, SOS, P-GFLG-Mce6, P-GFLG-SOS, P-(GFLG-Mce6)-Fab′, and P-(GFLG-SOS)-Fab′, when used as single agents or in binary combination, exhibited cytotoxic activities against OVCAR-3 cells, as determined using a modified MTT assay. The binding and internalization of P-(GFLG-Mce6)-Fab′ and P-(GFLG-SOS)-Fab′ by OVCAR-3 cells were visualized by confocal microscopy and flow cytometry. The results confirmed an enhanced biorecognition by OVCAR-3 cells of Fab′-targeted HPMA copolymer conjugates over nontargeted conjugates. The median-effect analysis and the determination of the combination index (CI) were used to describe the drug interaction and quantify the synergism, antagonism, or additivity in anticancer effects. The sequential combinations of SOS+Mce6 and P-GFLG-SOS+P-GFLG-Mce6 displayed very strong synergism to synergism in the entire range of cell inhibition levels (fa = 0.5 - 0.95). The P-(GFLG-SOS)-Fab′+P-(GFLG-Mce6)- Fab′ exhibited a strong synergism for fa values up to about 0.85, but showed synergistic effect and nearly additive effect at fa = 0.9 and 0.95, respectively. These observations support the continuation of in vivo investigations of these conjugates for the treatment of ovarian cancer. © 2008 American Chemical Society. 2018-07-12T02:17:23Z 2018-07-12T02:17:23Z 2008-09-01 Article Molecular Pharmaceutics. Vol.5, No.5 (2008), 696-709 10.1021/mp800006e 15438392 15438384 2-s2.0-56049117207 https://repository.li.mahidol.ac.th/handle/123456789/18865 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=56049117207&origin=inward |
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Biochemistry, Genetics and Molecular Biology Pharmacology, Toxicology and Pharmaceutics Jarunee Hongrapipat Pavla Kopečková Jihua Liu Sompol Prakongpan Jindřich Kopeček Combination chemotherapy and photodynamic therapy with Fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells |
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The biological activities of sequential combinations of anticancer drugs, SOS thiophene (SOS) and mesochlorin e6 monoethylenediamine (Mce6), in the form of free drugs, nontargeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer - drug conjugates, P-GFLG-Mce6 and P-GFLG-SOS (P is the HPMA copolymer backbone and GFLG is the glycylphenylalanylleucylglycine spacer), and Fab′-targeted HPMA copolymer - drug conjugates, P-(GFLG-Mce6)-Fab′ and P-(GFLG-SOS)-Fab′ (Fab′ from OV-TL 16 antibodies complementary to CD47), were evaluated against human ovarian carcinoma OVCAR-3 cells. Mce6, SOS, P-GFLG-Mce6, P-GFLG-SOS, P-(GFLG-Mce6)-Fab′, and P-(GFLG-SOS)-Fab′, when used as single agents or in binary combination, exhibited cytotoxic activities against OVCAR-3 cells, as determined using a modified MTT assay. The binding and internalization of P-(GFLG-Mce6)-Fab′ and P-(GFLG-SOS)-Fab′ by OVCAR-3 cells were visualized by confocal microscopy and flow cytometry. The results confirmed an enhanced biorecognition by OVCAR-3 cells of Fab′-targeted HPMA copolymer conjugates over nontargeted conjugates. The median-effect analysis and the determination of the combination index (CI) were used to describe the drug interaction and quantify the synergism, antagonism, or additivity in anticancer effects. The sequential combinations of SOS+Mce6 and P-GFLG-SOS+P-GFLG-Mce6 displayed very strong synergism to synergism in the entire range of cell inhibition levels (fa = 0.5 - 0.95). The P-(GFLG-SOS)-Fab′+P-(GFLG-Mce6)- Fab′ exhibited a strong synergism for fa values up to about 0.85, but showed synergistic effect and nearly additive effect at fa = 0.9 and 0.95, respectively. These observations support the continuation of in vivo investigations of these conjugates for the treatment of ovarian cancer. © 2008 American Chemical Society. |
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University of Utah |
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University of Utah Jarunee Hongrapipat Pavla Kopečková Jihua Liu Sompol Prakongpan Jindřich Kopeček |
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Article |
author |
Jarunee Hongrapipat Pavla Kopečková Jihua Liu Sompol Prakongpan Jindřich Kopeček |
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Jarunee Hongrapipat |
title |
Combination chemotherapy and photodynamic therapy with Fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells |
title_short |
Combination chemotherapy and photodynamic therapy with Fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells |
title_full |
Combination chemotherapy and photodynamic therapy with Fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells |
title_fullStr |
Combination chemotherapy and photodynamic therapy with Fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells |
title_full_unstemmed |
Combination chemotherapy and photodynamic therapy with Fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells |
title_sort |
combination chemotherapy and photodynamic therapy with fab' fragment targeted hpma copolymer conjugates in human ovarian carcinoma cells |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/18865 |
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1763493604467146752 |