α-Enolase–binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer

Abstract

Colorectal cancer is one of the most commonly diagnosed cancers and a leading cause of cancer mortality worldwide. Current treatment for colorectal cancer results in only limited success, and more effective therapeutic approaches are thus urgently needed. The development of new methods for early detection and effective treatments for cancer is contingent on the identification of biomarkers on the surface of cancer cells, as well as isolation of tumor-specific ligands with high binding affinity to such biomarkers. In vitro biopanning of a phage-displayed peptide library was used to identify specific peptides binding to human colorectal carcinoma cells. The targeting peptide pHCT74 showed the greatest potential for drug delivery in both in vitro and in vivo studies. The use of biotinylated peptides combined with an affinity trapping method and liquid chromatography-tandem mass spectrometry identified the target protein for the pHCT74 peptide as α-enolase. In animal model studies, combined pHCT74-conjugated liposomal doxorubicin (pHCT74-LD) and pHCT74-conjugated liposomal vinorelbine (pHCT74-sLV) therapy exhibited an enhanced antitumor effect and markedly extended the survival of mice with human colorectal cancer in subcutaneous and orthotopic models. Our findings indicate that α-enolase-targeted lipid nanoparticles have great potential for application in targeted drug delivery systems for colorectal cancer therapy.

Visualizing epithelial expression of EGFR in vivo with distal scanning side-viewing confocal endomicroscope

“…Also, peptides clear rapidly for reduced background and less biodistribution in non-target tissues30. Peptides have less potential for immunogenicity than antibodies, which allows for repetitive use31. We used Cy5.5, a NIR fluorophore, to label the peptide to maximize imaging depth, avoid hemoglobin absorption, reduce tissue scattering, and minimize autofluorescence background32.…”

Advancement and applications of peptide phage display technology in biomedical science

“…It can be performed in vitro against various types of cells, including cultured cell lines, primary cells isolated from animal models or human patients, or processed cells (fixed cells, activated cells etc.). Within the past ten years, several studies have focused on the in vitro biopanning of phage displayed peptide libraries using various cancer cell types [86][87][88][89][90] to identify cell-specific ligands [91].…”

“…Wu and co-workers aimed to overcome the problems outlined above by using biotinylated peptides to directly bind intact cells, and subsequent fixation of ligandreceptor complexes by cross-linking with 3,3′-dithiobis[sulfosuccinimidyl propionate] (DTSSP). After affinity trapping and LC-MS/MS analysis, the unknown target protein on the plasma membrane of the cells could be identified [89]. It is important to note that advances in peptide identification and subsequent receptor identification can lead to the discovery of important cellular targets that were previously unknown.…”

“…5). Remote loading methods, such as the ammonium sulfate method [110] and the pH gradient method [111], can encapsulate weak bases, such as doxorubicin or vinorelbine, into the liposomes with more than 95 % efficiency [89]. Schedule-dependent drugs, such as vinca alkaloids and topotecan, are reasonable candidates for liposomal delivery because of their effectiveness at enhancing the exposure time of cancer cells to therapeutic drug levels.…”

“…Increased IFP contributes to decreased transcapillary transport in tumors, which reduces uptake of drugs. This approach sidesteps the problem of high tumor IFP [89,113,114] and improves treatment effectiveness, thereby reducing incomplete tumor response, rapid disease relapse, and development of drug resistance due to suboptimal doses, which are often seen when using conventional chemotherapies.…”