Prostate cancer cell death produced by the co-delivery of Bcl-xL shRNA and doxorubicin using an aptamer-conjugated polyplex

Eunjung Kim, Yukyung Jung, Hyangtae Choi, Jaemoon Yang, Jin Suck Suh, Yong Min Huh, Kunhong Kim, Seungjoo Haam

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

We investigated the synergism between shRNAs against Bcl-xL and doxorubicin (DOX) using aptamer-conjugated polyplexes (APs) in combination cancer therapy. Synergistic and selective cancer cell death was achieved by AP-mediated co-delivery of very small amounts of DOX and Bcl-xL-specific shRNA, which simultaneously activated an intrinsic apoptotic pathway. A branched polyethyleneimine (PEI) was grafted to polyethylene glycol (PEI-PEG) to serve as a vehicle for shRNA delivery, and its surface was further conjugated with an anti-PSMA aptamer (APT) for the selective delivery of APs to prostate cancer cells that express prostate-specific membrane antigens (PSMA) on their cell surface. The APs were finally obtained after intercalation of DOX to form shRNA/PEI-PEG-APT/DOX conjugates. Cell viability assays and FACS analysis of GFP expression against PC3 (PSMA deficient) and LNCaP (PSMA overexpressed) cells demonstrated that the synthesized APs inhibited the growth of PSMA-abundant prostate cancer cells with strong cell selectivity. Consequently, IC50 values of APs loaded with both DOX and shRNA were approximately 17-fold less than those for the simple mixture of shRNA plus drug (shRNA/Lipofectamine + DOX). These results suggest that AP-mediated co-delivery of an anti-cancer drug and shRNA against Bcl-xL may widen the therapeutic window and allow for the selective destruction of cancer cells.

Original languageEnglish
Pages (from-to)4592-4599
Number of pages8
JournalBiomaterials
Volume31
Issue number16
DOIs
Publication statusPublished - 2010 Jun 1

Fingerprint

Cell death
Antigens
Doxorubicin
Small Interfering RNA
Prostatic Neoplasms
Cell Death
Membranes
Cells
Polyethyleneimine
Polyethylene glycols
Neoplasms
Intercalation
Assays
Pharmaceutical Preparations
Inhibitory Concentration 50
Cell Survival
human glutamate carboxypeptidase II
Therapeutics
Growth

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Kim, Eunjung ; Jung, Yukyung ; Choi, Hyangtae ; Yang, Jaemoon ; Suh, Jin Suck ; Huh, Yong Min ; Kim, Kunhong ; Haam, Seungjoo. / Prostate cancer cell death produced by the co-delivery of Bcl-xL shRNA and doxorubicin using an aptamer-conjugated polyplex. In: Biomaterials. 2010 ; Vol. 31, No. 16. pp. 4592-4599.
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Prostate cancer cell death produced by the co-delivery of Bcl-xL shRNA and doxorubicin using an aptamer-conjugated polyplex. / Kim, Eunjung; Jung, Yukyung; Choi, Hyangtae; Yang, Jaemoon; Suh, Jin Suck; Huh, Yong Min; Kim, Kunhong; Haam, Seungjoo.

In: Biomaterials, Vol. 31, No. 16, 01.06.2010, p. 4592-4599.

Research output: Contribution to journalArticle

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T1 - Prostate cancer cell death produced by the co-delivery of Bcl-xL shRNA and doxorubicin using an aptamer-conjugated polyplex

AU - Kim, Eunjung

AU - Jung, Yukyung

AU - Choi, Hyangtae

AU - Yang, Jaemoon

AU - Suh, Jin Suck

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AU - Kim, Kunhong

AU - Haam, Seungjoo

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