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

Authors
 Eunjung Kim  ;  Yukyung Jung  ;  Hyangtae Choi  ;  Jaemoon Yang  ;  Jin-Suck Suh  ;  Yong-Min Huh  ;  Kunhong Kim  ;  Seungjoo Haam 
Citation
 BIOMATERIALS, Vol.31(16) : 4592-4599, 2010 
Journal Title
 BIOMATERIALS 
ISSN
 0142-9612 
Issue Date
2010
MeSH
Antibiotics, Antineoplastic*/chemistry ; Antibiotics, Antineoplastic*/pharmacology ; Antibiotics, Antineoplastic*/therapeutic use ; Aptamers, Nucleotide*/chemistry ; Aptamers, Nucleotide*/pharmacology ; Aptamers, Nucleotide*/therapeutic use ; Cell Death/drug effects* ; Cell Line, Tumor ; Doxorubicin*/chemistry ; Doxorubicin*/pharmacology ; Doxorubicin*/therapeutic use ; Drug Carriers/chemistry ; Drug Carriers/metabolism ; Humans ; Male ; Materials Testing ; Polyethylene Glycols/chemistry ; Polyethylene Glycols/metabolism ; Polyethyleneimine/chemistry ; Polyethyleneimine/metabolism ; Prostatic Neoplasms/drug therapy* ; RNA, Small Interfering*/genetics ; RNA, Small Interfering*/metabolism ; bcl-X Protein*/genetics ; bcl-X Protein*/therapeutic use
Keywords
Combination cancer therapy ; Co-delivery ; Aptamer ; Doxorubicin ; Bcl-xL shRNA
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, IC(50) 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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0142961210002590
DOI
10.1016/j.biomaterials.2010.02.030
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Suh, Jin Suck(서진석) ORCID logo https://orcid.org/0000-0001-9455-9240
Yang, Jae Moon(양재문) ORCID logo https://orcid.org/0000-0001-7365-0395
Huh, Yong Min(허용민) ORCID logo https://orcid.org/0000-0002-9831-4475
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100684
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