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Enhanced cytotoxicity of saporin by polyamidoamine dendrimer conjugation and photochemical internalization
Author(s) -
Lai PingShan,
Pai ChinLing,
Peng ChengLiang,
Shieh MingJium,
Berg Kristian,
Lou PeiJen
Publication year - 2008
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.31760
Subject(s) - saporin , internalization , cytotoxicity , dendrimer , cytosol , biophysics , ribosome inactivating protein , chemistry , biochemistry , immunotoxin , cell , biology , in vitro , ribosome , rna , gene , enzyme
Because of the lack of membrane binding subunit, type I ribosome‐inactivating proteins (RIPs) are not very toxic to cells unless action is taken to allow for toxin internalization to the cytosol. To overcome the potential barriers that greatly hinder the cellular uptake and intracellular release of saporin, a type I RIP, we used generation 4 polyamidoamine (PAMAM) dendrimer as the carrier to improve its endocytic uptake, passive tumor targeting, and implemented the photochemical internalization (PCI) technology to facilitate its cytosolic release. Our results showed that the cellular uptake of saporin was increased after conjugation with the PAMAM dendrimer and the cytotoxic effect was improved by more than 1 order of magnitude. The cytotoxicity of free saporin and PAMAM‐saporin was further enhanced by the PCI technology. PCI changed the mechanism of cellular uptake of free saporin and then caused more saporin entering into the cells. After the PCI treatment, PAMAM‐saporin was not only internalized into the cytosol but also efficiently entered the nuclei. Our results indicated that conjugating to PAMAM dendrimer is a possible approach to enhance the cellular uptake of saporin. PCI is a promising technology to significantly enhance the cytotoxicity of both free saporin and PAMAM‐saporin. Combining both polymer conjugation and PCI approaches may improve the efficacy of RIPs in cancer therapy. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 87A: 147–155, 2008