Pharmaceutical Research

, Volume 27, Issue 11, pp 2296–2306 | Cite as

Multifunctional Tumor-Targeted Polymer-Peptide-Drug Delivery System for Treatment of Primary and Metastatic Cancers

  • Pooja Chandna
  • Jayant J. Khandare
  • Elizabeth Ber
  • Lorna Rodriguez-Rodriguez
  • Tamara Minko
Research Paper



In order to improve drug delivery to drug-resistant ovarian tumors, we constructed a multifunctional polymer-peptide-drug conjugate (PPDC) system for effective treatment of primary and metastatic ovarian cancers.


The PPDC consists of the poly(Ethylene Glycol) (PEG) polymeric carrier conjugated via citric acid spacers to anticancer drug (Camptothecin, CPT), tumor targeting moiety (LRHR, a synthetic analog of luteinizing hormone-releasing hormone) and a suppressor of cellular antiapoptotic defense (BH3 peptide). To test the conjugates in vitro and in vivo, cancer cells were isolated from tissue samples obtained from patients with ovarian primary tumor and metastatic malignant ascites.


It was found that cells isolated from malignant ascites were more aggressive in terms of tumor growth and more resistant to chemotherapy when compared with those isolated from primary tumors. PPDC containing two copies of drugs and peptides was most efficient in treatment of primary tumors and intraperitoneal metastases. Multiple treatments with this PPDC led to almost complete regression of primary tumor and prevented growth of malignant ascites.


The proposed multifunctional polymeric delivery system which consists of multiple copies of the drug and peptides demonstrated significantly higher antitumor activity in primary and metastatic cancers when compared with drug alone and PEG-CPT conjugate.


BH3 peptide camptothecin LHRH peptide PEG polymer proapoptotic peptide 



apoptotic protease activating factor 1


bicinchoninic acid

BH3 Peptide

CL2 Homology 3 Peptide


citric acid


Caspase 3


Caspase 9




fluorescein isothiocyanate


luteinizing hormone-releasing hormone


multidrug resistance


3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide


poly(Ethylene Glycol)


polymer-peptide-drug conjugate


reverse transcriptase-polymerase chain reaction





The research was supported in part by NIH Grants CA100098 and CA138533 from the National Cancer Institute.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Pooja Chandna
    • 1
  • Jayant J. Khandare
    • 1
  • Elizabeth Ber
    • 1
  • Lorna Rodriguez-Rodriguez
    • 2
    • 3
  • Tamara Minko
    • 1
    • 2
  1. 1.Department of Pharmaceutics, Ernest Mario School of PharmacyRutgers, The State University of New JerseyPiscatawayUSA
  2. 2.The Cancer Institute of New JerseyNew BrunswickUSA
  3. 3.Department of Obstetrics and GynecologyUMDNJ/Robert Wood Johnson Medical SchoolNew BrunswickUSA

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