Targeted proapoptotic anticancer drug delivery system

Pooja Chandna, Maha Saad, Yang Wang, Elizabeth Ber, Jayant Khandare, Alexandre A. Vetcher, Viatcheslav A. Soldatenkov, Tamara Minko

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)668-678
Number of pages11
JournalMolecular pharmaceutics
Volume4
Issue number5
DOIs
StatePublished - Sep 2007

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Keywords

  • Antitumor activity
  • Apoptosis
  • BH3
  • Camptothecin
  • Drug resistance
  • LHRH
  • Poly(ethylene glycol)
  • Tumor targeting

Fingerprint Dive into the research topics of 'Targeted proapoptotic anticancer drug delivery system'. Together they form a unique fingerprint.

Cite this