Combination chemotherapy and photodynamic therapy with fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells.

Molecular Pharmaceutics
Jarunee HongrapipatJindrich Kopecek

Abstract

The biological activities of sequential combinations of anticancer drugs, SOS thiophene (SOS) and mesochlorin e 6 monoethylenediamine (Mce 6), in the form of free drugs, nontargeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates, P-GFLG-Mce 6 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-Mce 6)-Fab' and P-(GFLG-SOS)-Fab' (Fab' from OV-TL16 antibodies complementary to CD47), were evaluated against human ovarian carcinoma OVCAR-3 cells. Mce 6, SOS, P-GFLG-Mce 6, P-GFLG-SOS, P-(GFLG-Mce 6)-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-Mce 6)-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...Continue Reading

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Citations

Jun 13, 2009·Chemical Communications : Chem Comm·Chalermchai KhemtongJinming Gao
Dec 10, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Acharaporn DuangjaiJindřich Kopeček
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Methods Mentioned

BETA
size exclusion chromatography
flow cytometry
fluorescence microscopy
confocal
confocal microscopy
immunoprecipitation

Software Mentioned

CompuSyn

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