GE11 peptide-conjugated nanoliposomes to enhance the combinational therapeutic efficacy of docetaxel and siRNA in laryngeal cancers

Abstract

In this study, dual therapeutic-loaded GE11 peptide-conjugated liposomes were developed and applied to enhance therapeutic efficacies of standard-of-care regimens for the treatment of laryngeal cancer. The therapeutic strategy used here was a combination treatment with the chemotherapeutic docetaxel (DTX) and siRNA against the ABCG2 gene that regulates multidrug resistance in many tumor types. Liposome-encapsulated DTX/ABCG2–siRNA molecules were targeted to recognize tumor cells of squamous morphology by conjugation to the EGFR-targeting ligand, GE11. Targeted, drug-infused liposomes were nanosized and exhibited controlled release of DTX. Presence of GE11 peptides on liposomal surfaces enhanced the quantities of liposomal constructs taken up by Hep-2 laryngeal cancer cells. GE11 peptide-conjugated liposomes also enhanced cytotoxic effects against Hep-2 laryngeal cancer cells when compared to treatment with free DTX, thereby reducing IC 50 values. Additionally, GE11 peptide-conjugated liposomes had significantly increased anti-tumor and apoptotic effects. Treatments with the GDSL nanoparticle formulation inhibited tumor growth in Hep-2 xenograft-bearing nude mouse models when compared to treatments with non-targeted NP constructs. Treatment of the mouse models with GE11 peptide-conjugated liposomes mitigated toxicities observed after treatment with free DTX. Taken together, liposomal encapsulation of DTX and ABCG2–siRNA improved the anti-tumor effects of treatment with free DTX in Hep-2 cell lines, and conjugation of GE11 peptides to liposomal constructs enhanced anti-tumor efficacies and specificities in laryngeal cancer cells.

GE11 Peptide as an Active Targeting Agent in Antitumor Therapy: A Minireview

“…Liposomes carrying active targeting agents can overcome the challenge of poor drug transfer from liposome to tumor and significantly improve DDS efficacy. GE11 has been studied among the several targeting ligands introduced in the literature, for example for estrone and tamoxifen targeting in breast cancer, or folate [ 42 , 65 , 66 , 67 , 68 ]. Pegylated liposomes carrying GE11 were prepared either as drug carriers or as contrast agents [ 42 , 68 ].…”

Activatable “Matryoshka” nanosystem delivery NgBR siRNA and control drug release for stepwise therapy and evaluate drug resistance cancer

“…In an acidic environment after 30 ​min, according to the result of 1 H-NMR, PEG began to dissociate, the charge of the nanosystem began to be positive. Compared with in the neutral environment, both the MONC-PPG and the MONC-PP system showed enhanced endocytosis, especially the MONC-PP, which illustrates the importance of charge reversal for promoting endocytosis [ 51 , [63] , [64] , [65] ].…”

Novel Peptide Therapeutic Approaches for Cancer Treatment

“…Treatment with docetaxel often results in upregulated expression of multidrug resistance genes, so the investigators also attached a small interfering RNA (siRNA) to the multidrug resistance gene, ABCG2, to the liposomes using electrostatic attraction. They found that by combining docetaxel with ABCG2-siRNA and using the GE11 to target the delivery, they were able to improve the antitumor efficacies and specificities in laryngeal cancer cells [ 68 ].…”