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Antitumor activity of poly(ethylene glycol)-camptothecin conjugate: the inhibition of tumor growth in vivo.
J Control Release. 2005 Dec 10; 110(1):90-102.JC

Abstract

Antitumor effect of poly(ethylene glycol)-camptothecin conjugate (PEG-CPT) was studied in the nude mouse model of human colon cancer xenografts. The animals were treated intravenously with 15 mg/kg of camptothecin (CPT) or PEG-CPT conjugate at equivalent CPT dose. Antitumor activity, apoptosis induction and caspase-dependent signaling pathways were studied 12, 24, 48 and 96 h after single injection. In addition, pharmacokinetics, tumor distribution and accumulation of PEG polymer labeled with green fluorescence protein (GFP) were studied. The data obtained showed that the conjugation of low molecular weight anticancer drug CPT with low solubility to high molecular weight water-soluble PEG polymer provides several advantages over the native drug. First, the conjugation improves drug pharmacokinetics in the blood and tumor. Second, such conjugation provides passive tumor targeting by the Enhanced Permeability and Retention (EPR) effect, increasing drug concentration in the tumor. Third, the coupling increases the bioavailability of CPT, induces apoptosis in tumor and, therefore, enhances anticancer activity of PEG-CPT. Thus, the use of macromolecular conjugate provided passive tumor targeting of the drug, improved pharmacokinetics and increased the stability of the drug during circulation. It offered better uptake by the targeted tumor cells and substantially enhanced apoptosis and antitumor activity of the conjugated drug in the tumor and decreased apoptosis in liver and kidney as compared with the native drug. All these characteristics make PEG-CPT conjugate an attractive anticancer drug for the effective chemotherapy of solid tumors.

Authors+Show Affiliations

Enzon Pharmaceuticals, Inc., Piscataway, NJ 08854, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16271793

Citation

Yu, Deshan, et al. "Antitumor Activity of Poly(ethylene Glycol)-camptothecin Conjugate: the Inhibition of Tumor Growth in Vivo." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 110, no. 1, 2005, pp. 90-102.
Yu D, Peng P, Dharap SS, et al. Antitumor activity of poly(ethylene glycol)-camptothecin conjugate: the inhibition of tumor growth in vivo. J Control Release. 2005;110(1):90-102.
Yu, D., Peng, P., Dharap, S. S., Wang, Y., Mehlig, M., Chandna, P., Zhao, H., Filpula, D., Yang, K., Borowski, V., Borchard, G., Zhang, Z., & Minko, T. (2005). Antitumor activity of poly(ethylene glycol)-camptothecin conjugate: the inhibition of tumor growth in vivo. Journal of Controlled Release : Official Journal of the Controlled Release Society, 110(1), 90-102.
Yu D, et al. Antitumor Activity of Poly(ethylene Glycol)-camptothecin Conjugate: the Inhibition of Tumor Growth in Vivo. J Control Release. 2005 Dec 10;110(1):90-102. PubMed PMID: 16271793.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antitumor activity of poly(ethylene glycol)-camptothecin conjugate: the inhibition of tumor growth in vivo. AU - Yu,Deshan, AU - Peng,Ping, AU - Dharap,Sonia S, AU - Wang,Yang, AU - Mehlig,Mary, AU - Chandna,Pooja, AU - Zhao,Hong, AU - Filpula,David, AU - Yang,Karen, AU - Borowski,Virna, AU - Borchard,Gerrit, AU - Zhang,Zhihua, AU - Minko,Tamara, Y1 - 2005/11/04/ PY - 2005/07/12/received PY - 2005/09/16/revised PY - 2005/09/22/accepted PY - 2005/11/8/pubmed PY - 2007/1/20/medline PY - 2005/11/8/entrez SP - 90 EP - 102 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 110 IS - 1 N2 - Antitumor effect of poly(ethylene glycol)-camptothecin conjugate (PEG-CPT) was studied in the nude mouse model of human colon cancer xenografts. The animals were treated intravenously with 15 mg/kg of camptothecin (CPT) or PEG-CPT conjugate at equivalent CPT dose. Antitumor activity, apoptosis induction and caspase-dependent signaling pathways were studied 12, 24, 48 and 96 h after single injection. In addition, pharmacokinetics, tumor distribution and accumulation of PEG polymer labeled with green fluorescence protein (GFP) were studied. The data obtained showed that the conjugation of low molecular weight anticancer drug CPT with low solubility to high molecular weight water-soluble PEG polymer provides several advantages over the native drug. First, the conjugation improves drug pharmacokinetics in the blood and tumor. Second, such conjugation provides passive tumor targeting by the Enhanced Permeability and Retention (EPR) effect, increasing drug concentration in the tumor. Third, the coupling increases the bioavailability of CPT, induces apoptosis in tumor and, therefore, enhances anticancer activity of PEG-CPT. Thus, the use of macromolecular conjugate provided passive tumor targeting of the drug, improved pharmacokinetics and increased the stability of the drug during circulation. It offered better uptake by the targeted tumor cells and substantially enhanced apoptosis and antitumor activity of the conjugated drug in the tumor and decreased apoptosis in liver and kidney as compared with the native drug. All these characteristics make PEG-CPT conjugate an attractive anticancer drug for the effective chemotherapy of solid tumors. SN - 0168-3659 UR - https://www.unboundmedicine.com/medline/citation/16271793/Antitumor_activity_of_poly_ethylene_glycol__camptothecin_conjugate:_the_inhibition_of_tumor_growth_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-3659(05)00504-3 DB - PRIME DP - Unbound Medicine ER -