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Molecular targeting of drug delivery systems to ovarian cancer by BH3 and LHRH peptides.
J Control Release. 2003 Aug 28; 91(1-2):61-73.JC

Abstract

Novel targeted proapoptotic anticancer drug delivery systems were developed and evaluated. Poly(ethyleneglycol) (PEG) conjugates were used as carriers. Camptothecin (CPT) was used as an anticancer agent-apoptosis inductor. Two types of molecular targets were investigated: (1) an extracellular membrane receptor specific to ovarian cancer and (2) intracellular controlling mechanisms of apoptosis. Synthetic peptides similar to luteinizing hormone-releasing hormone (LHRH) and BCL-2 homology 3 (BH3) peptide were used as a targeting moiety and a suppressor of cellular antiapoptotic defense, respectively. Three different conjugates (CPT-PEG, CPT-PEG-BH3 and CPT-PEG-LHRH) were synthesized and examined in A2780 human ovarian cancer cells. Cytotoxicity, expression of genes encoding BCL-2, BCL-XL, SMAC, APAF-1 proteins and caspases 3 and 9, the activity of caspases 3 and 9 and apoptosis induction were studied. Taken together the results indicate much higher cytotoxicity and apoptosis-inducing activity of PEG-CPT conjugates when compared to free CPT. Moreover, the effects of targeted CPT-PEG-BH3 and CPT-PEG-LHRH conjugates were more pronounced than the non-targeted PEG-CPT conjugate. The results confirmed the feasibility of this new two-tier molecular targeting strategy for enhancing the efficacy of cancer chemotherapy.

Authors+Show Affiliations

Department of Pharmaceutics, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12932638

Citation

Dharap, S S., et al. "Molecular Targeting of Drug Delivery Systems to Ovarian Cancer By BH3 and LHRH Peptides." Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 91, no. 1-2, 2003, pp. 61-73.
Dharap SS, Qiu B, Williams GC, et al. Molecular targeting of drug delivery systems to ovarian cancer by BH3 and LHRH peptides. J Control Release. 2003;91(1-2):61-73.
Dharap, S. S., Qiu, B., Williams, G. C., Sinko, P., Stein, S., & Minko, T. (2003). Molecular targeting of drug delivery systems to ovarian cancer by BH3 and LHRH peptides. Journal of Controlled Release : Official Journal of the Controlled Release Society, 91(1-2), 61-73.
Dharap SS, et al. Molecular Targeting of Drug Delivery Systems to Ovarian Cancer By BH3 and LHRH Peptides. J Control Release. 2003 Aug 28;91(1-2):61-73. PubMed PMID: 12932638.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular targeting of drug delivery systems to ovarian cancer by BH3 and LHRH peptides. AU - Dharap,S S, AU - Qiu,B, AU - Williams,G C, AU - Sinko,P, AU - Stein,S, AU - Minko,T, PY - 2003/8/23/pubmed PY - 2003/10/16/medline PY - 2003/8/23/entrez SP - 61 EP - 73 JF - Journal of controlled release : official journal of the Controlled Release Society JO - J Control Release VL - 91 IS - 1-2 N2 - Novel targeted proapoptotic anticancer drug delivery systems were developed and evaluated. Poly(ethyleneglycol) (PEG) conjugates were used as carriers. Camptothecin (CPT) was used as an anticancer agent-apoptosis inductor. Two types of molecular targets were investigated: (1) an extracellular membrane receptor specific to ovarian cancer and (2) intracellular controlling mechanisms of apoptosis. Synthetic peptides similar to luteinizing hormone-releasing hormone (LHRH) and BCL-2 homology 3 (BH3) peptide were used as a targeting moiety and a suppressor of cellular antiapoptotic defense, respectively. Three different conjugates (CPT-PEG, CPT-PEG-BH3 and CPT-PEG-LHRH) were synthesized and examined in A2780 human ovarian cancer cells. Cytotoxicity, expression of genes encoding BCL-2, BCL-XL, SMAC, APAF-1 proteins and caspases 3 and 9, the activity of caspases 3 and 9 and apoptosis induction were studied. Taken together the results indicate much higher cytotoxicity and apoptosis-inducing activity of PEG-CPT conjugates when compared to free CPT. Moreover, the effects of targeted CPT-PEG-BH3 and CPT-PEG-LHRH conjugates were more pronounced than the non-targeted PEG-CPT conjugate. The results confirmed the feasibility of this new two-tier molecular targeting strategy for enhancing the efficacy of cancer chemotherapy. SN - 0168-3659 UR - https://www.unboundmedicine.com/medline/citation/12932638/Molecular_targeting_of_drug_delivery_systems_to_ovarian_cancer_by_BH3_and_LHRH_peptides_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168365903002098 DB - PRIME DP - Unbound Medicine ER -