Star-shaped immunoglobulin-containing HPMA-based conjugates with doxorubicin for cancer therapy
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
17631976
DOI
10.1016/j.jconrel.2007.06.007
PII: S0168-3659(07)00289-1
Knihovny.cz E-resources
- MeSH
- Doxorubicin administration & dosage analogs & derivatives chemistry pharmacology MeSH
- Immunoglobulins administration & dosage chemistry MeSH
- Immunoconjugates administration & dosage chemistry MeSH
- Polymethacrylic Acids administration & dosage chemistry pharmacology MeSH
- Humans MeSH
- Lymphoma, T-Cell drug therapy MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Drug Carriers administration & dosage chemical synthesis chemistry MeSH
- Antibiotics, Antineoplastic administration & dosage chemistry pharmacology MeSH
- Drug Screening Assays, Antitumor MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Browser
- Doxorubicin MeSH
- Immunoglobulins MeSH
- Immunoconjugates MeSH
- Polymethacrylic Acids MeSH
- Drug Carriers MeSH
- Antibiotics, Antineoplastic MeSH
Synthesis and preliminary anticancer activity of new star-shaped immunoglobulin-containing polymer-doxorubicin (DOX) conjugates were investigated. The polymer precursors used for the synthesis of immunoglobulin-polymer-drug conjugates are based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, the anticancer drug DOX is attached to the immunoglobulin-modified polymer via a pH-sensitive hydrazone linkage. Such polymer-DOX conjugates are stable in aqueous solution at pH 7.4 (pH of blood plasma) and the drug is released in mildly acid environment at pH 5-5.5 (pH in endosomes or lysosomes of target cells). Semitelechelic copolymer chains are linked to the immunoglobulin via one-point attachment to avoid branching of the conjugate observed in our earlier studied systems. The cytostatic activity of the conjugates tested on several cancer cell lines was similar to that of free DOX.HCl and correlated with the sensitivity of a particular cell line to DOX. The star-shaped conjugates containing immunoglobulin showed a significantly higher antitumor activity in vivo than immunoglobulin-free non-targeted polymer conjugates when tested in mice bearing EL4 T-cell lymphoma.
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