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Tumor-specific targeting of an anticancer drug delivery system by LHRH peptide.
Proc Natl Acad Sci U S A. 2005 Sep 06; 102(36):12962-7.PN

Abstract

The central problem in cancer chemotherapy is the severe toxic side effects of anticancer drugs on healthy tissues. Invariably the side effects impose dose reduction, treatment delay, or discontinuance of therapy. To limit the adverse side effects of cancer chemotherapy on healthy organs, we proposed a drug delivery system (DDS) with specific targeting ligands for cancer cells. The proposed DDS minimizes the uptake of the drug by normal cells and enhances the influx and retention of the drug in cancer cells. This delivery system includes three main components: (i) an apoptosis-inducing agent (anticancer drug), (ii) a targeting moiety-penetration enhancer, and (iii) a carrier. We describe one of the variants of such a system, which utilizes camptothecin as an apoptosis-inducing agent and poly(ethylene glycol) as a carrier. Luteinizing hormone-releasing hormone (LHRH) was used as a targeting moiety (ligand) to LHRH receptors that are overexpressed in the plasma membrane of several types of cancer cells and are not expressed detectably in normal visceral organs. The results showed that the use of LHRH peptide as a targeting moiety in the anticancer DDS substantially enhanced the efficacy of chemotherapy, led to amplified apoptosis induction in the tumor, and minimized the side effects of the anticancer drug on healthy organs. The LHRH receptor targeting DDS did not show in vivo pituitary toxicity and did not significantly influence the time course or the plasma concentration of luteinizing hormone and its physiological effects on the reproductive functions of mice.

Authors+Show Affiliations

Department of Pharmaceutics, Rutgers, The State University of New Jersey, 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 available

Pub Type(s)

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

Language

eng

PubMed ID

16123131

Citation

Dharap, S S., et al. "Tumor-specific Targeting of an Anticancer Drug Delivery System By LHRH Peptide." Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 36, 2005, pp. 12962-7.
Dharap SS, Wang Y, Chandna P, et al. Tumor-specific targeting of an anticancer drug delivery system by LHRH peptide. Proc Natl Acad Sci U S A. 2005;102(36):12962-7.
Dharap, S. S., Wang, Y., Chandna, P., Khandare, J. J., Qiu, B., Gunaseelan, S., Sinko, P. J., Stein, S., Farmanfarmaian, A., & Minko, T. (2005). Tumor-specific targeting of an anticancer drug delivery system by LHRH peptide. Proceedings of the National Academy of Sciences of the United States of America, 102(36), 12962-7.
Dharap SS, et al. Tumor-specific Targeting of an Anticancer Drug Delivery System By LHRH Peptide. Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12962-7. PubMed PMID: 16123131.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor-specific targeting of an anticancer drug delivery system by LHRH peptide. AU - Dharap,S S, AU - Wang,Y, AU - Chandna,P, AU - Khandare,J J, AU - Qiu,B, AU - Gunaseelan,S, AU - Sinko,P J, AU - Stein,S, AU - Farmanfarmaian,A, AU - Minko,T, Y1 - 2005/08/25/ PY - 2005/8/27/pubmed PY - 2005/11/3/medline PY - 2005/8/27/entrez SP - 12962 EP - 7 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 102 IS - 36 N2 - The central problem in cancer chemotherapy is the severe toxic side effects of anticancer drugs on healthy tissues. Invariably the side effects impose dose reduction, treatment delay, or discontinuance of therapy. To limit the adverse side effects of cancer chemotherapy on healthy organs, we proposed a drug delivery system (DDS) with specific targeting ligands for cancer cells. The proposed DDS minimizes the uptake of the drug by normal cells and enhances the influx and retention of the drug in cancer cells. This delivery system includes three main components: (i) an apoptosis-inducing agent (anticancer drug), (ii) a targeting moiety-penetration enhancer, and (iii) a carrier. We describe one of the variants of such a system, which utilizes camptothecin as an apoptosis-inducing agent and poly(ethylene glycol) as a carrier. Luteinizing hormone-releasing hormone (LHRH) was used as a targeting moiety (ligand) to LHRH receptors that are overexpressed in the plasma membrane of several types of cancer cells and are not expressed detectably in normal visceral organs. The results showed that the use of LHRH peptide as a targeting moiety in the anticancer DDS substantially enhanced the efficacy of chemotherapy, led to amplified apoptosis induction in the tumor, and minimized the side effects of the anticancer drug on healthy organs. The LHRH receptor targeting DDS did not show in vivo pituitary toxicity and did not significantly influence the time course or the plasma concentration of luteinizing hormone and its physiological effects on the reproductive functions of mice. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/16123131/Tumor_specific_targeting_of_an_anticancer_drug_delivery_system_by_LHRH_peptide_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=16123131 DB - PRIME DP - Unbound Medicine ER -