Self‐Assembled Bifunctional Peptide as Effective Drug Delivery Vector with Powerful Antitumor Activity

Abstract

E‐cadherin/catenin complex is crucial for cancer cell migration and invasion. The histidine‐alanine‐valine (HAV) sequence has been shown to inhibit a variety of cadherin‐based functions. In this study, by fusing HAV and the classical tumor‐targeting Arg‐Gly‐Asp (RGD) motif and Asn‐Gly‐Arg (NGR) motif to the apoptosis‐inducing peptide sequence‐AVPIAQK, a bifunctional peptide has been constructed with enhanced tumor targeting and apoptosis effects. This peptide is further processed as a nanoscale vector to encapsulate the hydrophobic drug docetaxel (DOC). Bioimaging analysis shows that peptide nanoparticles can penetrate into xenograft tumor cells with a significantly long retention in tumors and high tumor targeting specificity. In vivo, DOC/peptide NPs are substantially more effective at inhibiting tumor growth and prolonging survival compared with DOC control. Together, the findings of this study suggest that DOC/peptide NPs may have promising applications in pulmonary carcinoma therapy.

Peptide‐Based Supramolecular Nanodrugs as a New Generation of Therapeutic Toolboxes against Cancer

“…[66] This peptide was used as a nanocarrier to deliver the chemotherapeutic drug DOC. They target receptors on the surface of tumor cells or the tumor microenvironment, such as the tumor vasculature.…”

Recent Advances in Targeted Tumor Chemotherapy Based on Smart Nanomedicines

“…Tripeptide of Asn–Gly–Arg (NGR) sequence is another targeting peptide that selectively binds to CD13/aminopeptidase N (APN), which was overexpressed in tumor vasculature and certain tumor cells . NGR‐containing peptides have been exploited to deliver different antitumor agents . In these systems, drugs modified with NGR displayed enhanced antitumor effects against tumor cells but lower toxicity to normal cells.…”

Conjugates of Cell Adhesion Peptides for Therapeutics and Diagnostics Against Cancer and Autoimmune Diseases

“…A combination of HAV, NGRRGD, and AVPIAQK sequences was implemented in HRK-19 peptide (HAVRNGRRGDGGAVPIAQK) to target the DOC-bearing nanoparticles to tumor cells. The HAV, NGR, and RGD sequences were used to target cadherin, α V β 3 integrins, and aminopeptidase-N (CD13), respectively, on tumor blood vessels [94]. At 5 nM dose, the apoptotic index of DOC-loaded-HRK-19 peptide nanoparticles was significantly higher than DOC alone on treated A549 cancer cells.…”

“…At 5 nM dose, the apoptotic index of DOC-loaded-HRK-19 peptide nanoparticles was significantly higher than DOC alone on treated A549 cancer cells. Nanoparticles decorated with HRK-19 peptide (DOC-loaded-HRK-19) penetrated xenograft tumor with high efficiency in vivo, with slightly better efficacy than that of drug alone, in extending animal survival [94]. The nanoparticle efficacy was significantly better than saline and HRK-19 alone in suppressing A549 tumor growth and extending animal survival [94].…”

“…Nanoparticles decorated with HRK-19 peptide (DOC-loaded-HRK-19) penetrated xenograft tumor with high efficiency in vivo, with slightly better efficacy than that of drug alone, in extending animal survival [94]. The nanoparticle efficacy was significantly better than saline and HRK-19 alone in suppressing A549 tumor growth and extending animal survival [94]. DOC-loaded-HRK-19 nanoparticles also significantly suppressed pulmonary tumor metastasis of A549 cells, compared with saline and peptide alone.…”