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Targeted proapoptotic anticancer drug delivery system.
Mol Pharm. 2007 Sep-Oct; 4(5):668-78.MP

Abstract

A novel targeted proapoptotic anticancer drug delivery system (DDS) was developed and evaluated both in vitro and in vivo. The system contains poly(ethylene glycol) polymer (PEG) as a carrier, camptothecin (CPT) as an anticancer drug/cell death inducer, a synthetic analogue of luteinizing hormone-releasing hormone (LHRH) peptide as a targeting moiety/penetration enhancer, and a synthetic analogue of BCL2 homology 3 domain (BH3) peptide as a suppressor of cellular antiapoptotic defense. The design of the multicomponent DDS allowed for a conjugation of one or two copies of each active ingredient (CPT, LHRH, and BH3) to one molecule of PEG carrier. The complex structure of the PEG conjugates was visualized at nanometer resolution using atomic force microscopy. We found that the ligand-targeted DDS for cancer cells preferentially accumulated in the tumor and allowed the delivery of active ingredients into the cellular cytoplasm and nuclei of cancer cells. Simultaneous apoptosis induction through the caspase-dependent signaling pathway and inhibition of cellular antiapoptotic defense by the suppression of BCL2 protein enhanced cytotoxicity and antitumor activity of the entire DDS to a level which could not be achieved by individual components applied separately. The DDS containing two copies of each active component (CPT, LHRH, and BH3) per molecule of PEG polymer had the highest anticancer efficiency in vitro and in vivo.

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 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

17685579

Citation

Chandna, Pooja, et al. "Targeted Proapoptotic Anticancer Drug Delivery System." Molecular Pharmaceutics, vol. 4, no. 5, 2007, pp. 668-78.
Chandna P, Saad M, Wang Y, et al. Targeted proapoptotic anticancer drug delivery system. Mol Pharm. 2007;4(5):668-78.
Chandna, P., Saad, M., Wang, Y., Ber, E., Khandare, J., Vetcher, A. A., Soldatenkov, V. A., & Minko, T. (2007). Targeted proapoptotic anticancer drug delivery system. Molecular Pharmaceutics, 4(5), 668-78.
Chandna P, et al. Targeted Proapoptotic Anticancer Drug Delivery System. Mol Pharm. 2007 Sep-Oct;4(5):668-78. PubMed PMID: 17685579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeted proapoptotic anticancer drug delivery system. AU - Chandna,Pooja, AU - Saad,Maha, AU - Wang,Yang, AU - Ber,Elizabeth, AU - Khandare,Jayant, AU - Vetcher,Alexandre A, AU - Soldatenkov,Viatcheslav A, AU - Minko,Tamara, Y1 - 2007/08/09/ PY - 2007/8/10/pubmed PY - 2007/12/13/medline PY - 2007/8/10/entrez SP - 668 EP - 78 JF - Molecular pharmaceutics JO - Mol Pharm VL - 4 IS - 5 N2 - A novel targeted proapoptotic anticancer drug delivery system (DDS) was developed and evaluated both in vitro and in vivo. The system contains poly(ethylene glycol) polymer (PEG) as a carrier, camptothecin (CPT) as an anticancer drug/cell death inducer, a synthetic analogue of luteinizing hormone-releasing hormone (LHRH) peptide as a targeting moiety/penetration enhancer, and a synthetic analogue of BCL2 homology 3 domain (BH3) peptide as a suppressor of cellular antiapoptotic defense. The design of the multicomponent DDS allowed for a conjugation of one or two copies of each active ingredient (CPT, LHRH, and BH3) to one molecule of PEG carrier. The complex structure of the PEG conjugates was visualized at nanometer resolution using atomic force microscopy. We found that the ligand-targeted DDS for cancer cells preferentially accumulated in the tumor and allowed the delivery of active ingredients into the cellular cytoplasm and nuclei of cancer cells. Simultaneous apoptosis induction through the caspase-dependent signaling pathway and inhibition of cellular antiapoptotic defense by the suppression of BCL2 protein enhanced cytotoxicity and antitumor activity of the entire DDS to a level which could not be achieved by individual components applied separately. The DDS containing two copies of each active component (CPT, LHRH, and BH3) per molecule of PEG polymer had the highest anticancer efficiency in vitro and in vivo. SN - 1543-8384 UR - https://www.unboundmedicine.com/medline/citation/17685579/Targeted_proapoptotic_anticancer_drug_delivery_system_ L2 - https://doi.org/10.1021/mp070053o DB - PRIME DP - Unbound Medicine ER -