Antibody-targeted polymer-doxorubicin conjugates with pH-controlled activation
Language English Country Great Britain, England Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
15621674
DOI
10.1080/10611860400011869
PII: WM4GKH10N6NPL33Y
Knihovny.cz E-resources
- MeSH
- Antilymphocyte Serum administration & dosage MeSH
- Doxorubicin administration & dosage chemistry MeSH
- Chemistry, Pharmaceutical MeSH
- Hydrogen-Ion Concentration MeSH
- Drug Delivery Systems methods MeSH
- Lymphoma, T-Cell drug therapy MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Polymers administration & dosage chemistry MeSH
- Antineoplastic Agents administration & dosage chemistry MeSH
- Drug Screening Assays, Antitumor methods MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Antilymphocyte Serum MeSH
- Doxorubicin MeSH
- Polymers MeSH
- Antineoplastic Agents MeSH
The paper is dealing with the synthesis and properties of new non-targeted or antibody-targeted polymer drug conjugates, bearing doxorubicin (DOX) attached via a spacer susceptible to pH-controlled hydrolysis (hydrazone conjugates), designed as anticancer drugs facilitating site-specific therapy. These conjugates are stable in a pH 7.4 buffer, modeling conditions during transport in the body, but release DOX and activate it inside target cells as a result of pH changes when going from outside to inside the cells. Conjugates containing an antibody directed against T lymphocytes bind effectively and specifically T cell lymphoma EL 4 cells. Cytotoxicity of the hydrazone conjugates is higher than that of classic conjugates, depending on the detailed structure of the polymer, the spacer between the drug and polymer carrier and method of antibody conjugation. Cytotoxicity of some of the conjugates is comparable even with that of the free drug. In both protective and therapeutic regimes of drug administration, the in vivo anti-tumor activity of the conjugates containing DOX was enhanced with long-term survivors (T-cell lymphoma EL 4, C57BL/6 mice) in comparison with much less effective free DOX or a classic P(N-(2-hydroxypropyl)methacrylamide)HPMA-DOX conjugate (already clinically tested).
References provided by Crossref.org
Singlet Oxygen In Vivo: It Is All about Intensity-Part 2
Structure-to-Efficacy Relationship of HPMA-Based Nanomedicines: The Tumor Spheroid Penetration Study
