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

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141 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

Bibliographical note

Funding Information:
This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health &Welfare, Republic of Korea ( A085136 ). This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) ( No. 2007-04045 ). This study was supported by a faculty research grant of Yonsei University College of Medicine ( 6-2007-0198 ).

All Science Journal Classification (ASJC) codes

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

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