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Novel polymeric prodrug with multivalent components for cancer therapy.
J Pharmacol Exp Ther. 2006 Jun; 317(3):929-37.JP

Abstract

We designed, synthesized, and evaluated in vitro and in vivo a novel targeted anticancer polymeric prodrug containing multiple copies of tumor targeting moiety [synthetic luteinizing hormone-releasing hormone (LHRH) peptide, analog of LHRH] and anticancer drug (camptothecin). One, two, or three molecules of the targeting peptide and anticancer drug were covalently conjugated with bis(2-carboxyethyl) polyethylene glycol polymer using citric acid as a multivalent spacer. We showed that LHRH peptide was bound to extracellular receptors and localized in plasma membrane of cancer cells. The designed tumor-targeted prodrug increased the solubility of anticancer drug and offered cytoplasmic and/or nuclear delivery of drug to cancer cells expressing LHRH receptors. The multicomponent prodrug containing three copies of the targeting peptide and drug was almost 100 times more cytotoxic and substantially had enhanced antitumor activity compared with the analogous nontargeted prodrug and prodrugs containing one or two copies of active components.

Authors+Show Affiliations

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16469865

Citation

Khandare, Jayant J., et al. "Novel Polymeric Prodrug With Multivalent Components for Cancer Therapy." The Journal of Pharmacology and Experimental Therapeutics, vol. 317, no. 3, 2006, pp. 929-37.
Khandare JJ, Chandna P, Wang Y, et al. Novel polymeric prodrug with multivalent components for cancer therapy. J Pharmacol Exp Ther. 2006;317(3):929-37.
Khandare, J. J., Chandna, P., Wang, Y., Pozharov, V. P., & Minko, T. (2006). Novel polymeric prodrug with multivalent components for cancer therapy. The Journal of Pharmacology and Experimental Therapeutics, 317(3), 929-37.
Khandare JJ, et al. Novel Polymeric Prodrug With Multivalent Components for Cancer Therapy. J Pharmacol Exp Ther. 2006;317(3):929-37. PubMed PMID: 16469865.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel polymeric prodrug with multivalent components for cancer therapy. AU - Khandare,Jayant J, AU - Chandna,Pooja, AU - Wang,Yang, AU - Pozharov,Vitaly P, AU - Minko,Tamara, Y1 - 2006/02/09/ PY - 2006/2/14/pubmed PY - 2006/6/27/medline PY - 2006/2/14/entrez SP - 929 EP - 37 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 317 IS - 3 N2 - We designed, synthesized, and evaluated in vitro and in vivo a novel targeted anticancer polymeric prodrug containing multiple copies of tumor targeting moiety [synthetic luteinizing hormone-releasing hormone (LHRH) peptide, analog of LHRH] and anticancer drug (camptothecin). One, two, or three molecules of the targeting peptide and anticancer drug were covalently conjugated with bis(2-carboxyethyl) polyethylene glycol polymer using citric acid as a multivalent spacer. We showed that LHRH peptide was bound to extracellular receptors and localized in plasma membrane of cancer cells. The designed tumor-targeted prodrug increased the solubility of anticancer drug and offered cytoplasmic and/or nuclear delivery of drug to cancer cells expressing LHRH receptors. The multicomponent prodrug containing three copies of the targeting peptide and drug was almost 100 times more cytotoxic and substantially had enhanced antitumor activity compared with the analogous nontargeted prodrug and prodrugs containing one or two copies of active components. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16469865/Novel_polymeric_prodrug_with_multivalent_components_for_cancer_therapy_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=16469865 DB - PRIME DP - Unbound Medicine ER -