Enhanced cytotoxicity of saporin by polyamidoamine dendrimer conjugation and photochemical internalization
Journal
Journal of Biomedical Materials Research - Part A
Journal Volume
87
Journal Issue
1
Pages
147-155
Date Issued
2008
Author(s)
Abstract
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.
SDGs
Other Subjects
Cell membranes; Computer peripheral equipment; Technology; Cancer therapies; Cancer therapy; Cellular uptake; Cytosol; Cytosolic; Cytotoxic effects; Membrane binding; Order-of magnitudes; PAMAM dendrimer; Photochemical internalization; Polyamidoamine dendrimer; Polymer conjugation; Potential barriers; Ribosome-inactivating protein; Ribosome-inactivating proteins; Saporin; Toxin internalization; Tumor targeting; Interfaces (computer); dendrimer; polyamidoamine; ribosome inactivating protein; saporin; article; cancer therapy; cell transport; confocal microscopy; conjugation; controlled study; cytotoxicity; drug release; endocytosis; human; human cell; photochemical internalization; photodynamic therapy; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cytosol; Dendrimers; Drug Carriers; Endocytosis; Humans; Microscopy, Confocal; Nylons; Photochemistry; Photochemotherapy; Photosensitizing Agents; Ribosome Inactivating Proteins, Type 1
Type
journal article