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Multifunctional tumor-targeted polymer-peptide-drug delivery system for treatment of primary and metastatic cancers.
Pharm Res. 2010 Nov; 27(11):2296-306.PR

Abstract

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

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Authors+Show Affiliations

Chandna P
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854-8020, USA.
Khandare JJ
No affiliation info available
Ber E
No affiliation info available
Rodriguez-Rodriguez L
No affiliation info available
Minko T
No affiliation info available

MeSH

AnimalsAntineoplastic AgentsApoptosisBase SequenceDNA PrimersDrug CarriersFemaleHumansMiceMice, NudeNeoplasm MetastasisNeoplasmsPeptidesPolymersReverse Transcriptase Polymerase Chain ReactionSignal Transduction

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20700631

Citation

Chandna, Pooja, et al. "Multifunctional Tumor-targeted Polymer-peptide-drug Delivery System for Treatment of Primary and Metastatic Cancers." Pharmaceutical Research, vol. 27, no. 11, 2010, pp. 2296-306.
Chandna P, Khandare JJ, Ber E, et al. Multifunctional tumor-targeted polymer-peptide-drug delivery system for treatment of primary and metastatic cancers. Pharm Res. 2010;27(11):2296-306.
Chandna, P., Khandare, J. J., Ber, E., Rodriguez-Rodriguez, L., & Minko, T. (2010). Multifunctional tumor-targeted polymer-peptide-drug delivery system for treatment of primary and metastatic cancers. Pharmaceutical Research, 27(11), 2296-306. https://doi.org/10.1007/s11095-010-0235-2
Chandna P, et al. Multifunctional Tumor-targeted Polymer-peptide-drug Delivery System for Treatment of Primary and Metastatic Cancers. Pharm Res. 2010;27(11):2296-306. PubMed PMID: 20700631.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multifunctional tumor-targeted polymer-peptide-drug delivery system for treatment of primary and metastatic cancers. AU - Chandna,Pooja, AU - Khandare,Jayant J, AU - Ber,Elizabeth, AU - Rodriguez-Rodriguez,Lorna, AU - Minko,Tamara, Y1 - 2010/08/11/ PY - 2010/05/03/received PY - 2010/07/28/accepted PY - 2010/8/12/entrez PY - 2010/8/12/pubmed PY - 2011/2/18/medline SP - 2296 EP - 306 JF - Pharmaceutical research JO - Pharm Res VL - 27 IS - 11 N2 - PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. SN - 1573-904X UR - https://www.unboundmedicine.com/medline/citation/20700631/Multifunctional_tumor_targeted_polymer_peptide_drug_delivery_system_for_treatment_of_primary_and_metastatic_cancers_ L2 - https://doi.org/10.1007/s11095-010-0235-2 DB - PRIME DP - Unbound Medicine ER -