The potential use of many promising novel drugs is limited by their inability to specifically reach their site of action after intravenous administration, without secondary effects on healthy tissues. In order to remediate this problem, the protein transferrin (Tf) has been extensively studied as a targeting molecule for the transport of drug and gene delivery systems to the brain and cancer cells. A wide range of delivery approaches have been developed to target the Tf receptor and they have already improved the specific delivery of Tf-bearing therapeutic agents to their site of action. This review provides a summary of the numerous delivery strategies used to target the Tf receptor and focuses on recent therapeutic advances.

This version is available at https://strathprints.strath.ac.uk/42676/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. would be an attractive anti-cancer treatment strategy, however the lack of suitable carrier systems able to selectively deliver therapeutic genes to tumors has so far limited this investigation. Given that transferrin receptors are overexpressed on prostate cancer cells, the purpose of this study is to determine whether transferrinbearing dendriplex encoding TNF±, TRAIL and IL-12 would suppress the growth of prostate cancer cell lines in vitro and in vivo. TITLE Materials & Methods:Transferrin-bearing dendriplexes encoding TNF±, TRAIL and IL-12 were intravenously administered to mice bearing subcutaneous PC-3 and DU145 tumors. Results:The administration of the DAB-Tf dendriplex encoding TNF± resulted in tumor suppression for 60% of PC-3 and 50% of DU145 prostate tumors. Conclusions:These dendriplexes hold great potential as a novel approach for prostate cancer therapy. KEYWORDS 4 MATERIALS & METHODS Cell lines and reagents Preparation of transferrin-bearing polypropylenimine dendrimerGeneration 3-diaminobutyric polypropylenimine dendrimer (DAB, 24 mg) was conjugated to transferrin (Tf, 6 mg) by cross-linking with dimethylsuberimidate (DMSI, 12 mg) in triethanolamine HCl buffer (pH 7.4, 2 mL), as previously described 8 Statistical AnalysisResults were expressed as means ± standard error of the mean (S.E.M). Statistical significance was assessed by one-way analysis of variance (ANOVA) and Bonferroni multiple comparison post-test (GraphPad Prism software). P values lower than 0.05 were considered statistically different. 9 RESULTS Cellular uptake of DNAConfocal microscopy experiments confirmed that Cy3-labelled DNA was taken up by PC-3, DU145 and LNCaP cells (Figure 1). The fluorescently-labeled DNA was found to be disseminated in the cytoplasm following treatment with DAB-Tf and DAB dendriplexes in the three teste...