Redox-Sensitive Nanocomplex for Targeted Delivery of Melittin.

Bei Cheng,Peisheng Xu

doi:10.3390/toxins12090582

Bei Cheng, Peisheng Xu

Open Access

https://doi.org/10.3390/toxins12090582

Copy DOI

Abstract

Although peptide therapeutics have been explored for decades, the successful delivery of potent peptides in vitro and in vivo remains challenging due to the poor stability, low cell permeability, and off-target effects. We developed a redox sensitive polymer-based nanocomplex which can efficiently and stably deliver the peptide drug melittin for cancer therapy. The nanocomplex selectively targets cancer cells through lactobionic acid mediated endocytosis and releases melittin intracellularly upon the trigger of elevated redox potential. In vivo study proved that the targeted nanocomplex shows excellent potency in inhibiting tumor growth in a xenograft colon cancer mouse model. Thus, the polymer/melittin nanocomplexes will provide a new approach for melittin based cancer therapy.

Highlights

Peptide-based drugs, which usually have less than 50 amino acids, hold a high potential for treating various diseases
Melittin was successfully delivered into cytosol and released under the acidic pH and high
We successfully developed a polymer/melittin based nanocomplex to evaluate its

Summary

Introduction

Peptide-based drugs, which usually have less than 50 amino acids, hold a high potential for treating various diseases. Some peptide-based drugs have successfully entered the market, such as cyclosporine, which is routinely used after organ transplantation to reduce the activity of the immune system [1]. Some peptides can be utilized as a cytosolic agent. The last decade has witnessed the exponential growth of many peptide drugs entering clinical trials [4]. Peptides hold many advantages for anticancer medications due to their high potency and a broad range of targets. The available cyclosporine preparations showed a low bioavailability, high variation between patients, and the inability to obtain both effective and safe doses [1]

Methods

Results

Conclusion