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Study summary · research use only

P53-Derived peptides conjugation to PEI: an approach to producing versatile and highly efficient targeted gene delivery carriers into cancer cells

Study · human · Expert opinion on drug delivery · 2016 · DOI 10.1517/17425247.2016.1126245 · PMID 26654047

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

In this in vitro study using nine cell lines, including MCF-7 and NIH-3T3 (species not specified for the lines), a targeted gene delivery system conjugating p53-derived peptides PNC 27 and PNC 28 to PEI was developed, targeting HDM-2 on the surface of cancer cells. The abstract reports that immunocytochemistry and flow cytometry were used to identify HDM-2-expressing cells, and that peptide conjugation to vectors was confirmed by reverse-phase HPLC. Physicochemical properties of vector/DNA complexes, including particle size, surface charge, and DNA condensation ability, were measured. In transfection studies using luciferase, pEGFP, and shRNA plasmids against Bcl-XL mRNA, the abstract reports that PNC peptide conjugation was associated with gene delivery and shRNA-based gene silencing selectively into cancer cells, as assessed by real-time PCR and western blot.

Abstract

Targeted delivery of cytotoxic drugs or therapeutic antisense RNAs into specific cells is a major bottleneck in cancer therapy. To overcome this problem and improve the specificity for cancer cells, we describe a new-targeted delivery system using p53-derived peptides, namely PNC 27 and PNC 28. These peptides target HDM-2 on the surface of cancer cells. HDM-2 is overexpressed on the surface of cancerous cells, but not present on the untransformed cells. To determine HDM-2-expressing cells, we used immunocytochemistry and flow cytometry analysis on nine cell lines including MCF-7 and NIH-3t3. Conjugation of peptides to vectors was confirmed using reverse-phase high-pressure liquid chromatography (RP-HPLC). Physicochemical properties of vector/DNA complexes including particle size, surface charge and DNA condensation ability were determined. In transfection studies, three plasmids were used including luciferase, pEGFP and shRNA plasmid against Bcl-XL mRNA. The level of Bcl-XL expression was determined by real-time PCR and western blot techniques. The results of gene delivery and shRNA-based gene silencing studies indicated that conjugation of PNC peptides could enhance gene delivery efficiently with high-targeted activity exclusively into cancer cells. Our results strongly indicated that this targeting system could be utilized as an efficient targeting method for most cancer cells.

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