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PNC27 anticancer peptide as targeting ligand significantly improved antitumor efficacy of Doxil in HDM2-expressing cells

Study · Nanomedicine (London, England) · 2017 · DOI 10.2217/nnm-2017-0069 · PMID 28565974

Plain-language summary

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

This study examined whether PNC27, a peptide corresponding to residues 12-26 of p53 with affinity for HDM2 protein, could serve as a targeting ligand for Doxil. Doxil liposomes were postinserted with 25, 50, 100, or 200 PNC27 peptides per liposome, tested by flow cytometry and confocal analysis in HDM2-positive C26 colon carcinoma and HDM2-negative B16F0 melanoma cells, and in vivo in BALB/c mice bearing C26 tumors and C57BL/6 mice bearing B16F0 tumors. PNC27-Doxil showed increased cellular uptake and cytotoxicity in C26 cells compared with Doxil alone, and PNC27-Doxil (100 PNC27 peptide) was associated with improved antitumor activity of Doxil without altered biodistribution in C26 tumors; this was not observed in B16F0 cells. The authors describe PNC27 as a candidate targeting ligand for Doxil in HDM2-positive cancers.

Abstract

To investigate the potential of PNC27 peptide, 12-26 of p53 with high affinity for HDM2 protein, as targeting ligand for Doxil to improve its antitumor activity. Doxil postinserted with 25, 50, 100 and 200 PNC27 peptides per liposome. Flow cytometry and confocal analysis were performed on C26 colon carcinoma (HDM2 positive) and B16F0 melanoma (HDM2 negative) cells. In vivo studies were performed on BALB/c mice bearing C26 and C57BL/6 mice bearing B16F0 tumor models. PNC27-Doxil showed significant cellular uptake and cytotoxicity in C26 cells compared with Doxil. PNC27-Doxil (100 PNC27 peptide) significantly improved therapeutic efficacy of Doxil without compromising its biodistribution in C26 tumor. However, these results were not observed in B16F0 cells. PNC27 is a promising targeting ligand for Doxil against HDM2-positive cancers.

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