Injectable pH and redox dual responsive hydrogels based on self-assembled peptides for anti-tumor drug delivery

Abstract

Traditional anti-tumor drugs still have some shortcomings, such as low solubility, poor selectivity and poor bioavailability, which decrease their anti-tumor efficacy and aggravate systemic toxicity and side effects. In this paper, pH/redox dual responsive IC1-R peptide hydrogels were designed as drug delivery materials for the anti-tumor drug paclitaxel (PTX). The physical and chemical properties of drug-loaded IC1-R peptide hydrogels were characterized by pH/redox sensitivity, drug release, physical description, encapsulation rate, circular dichroism, electron transmission microscopy, and rheological tests. In vitro cytotoxicity and in vivo efficacy were studied to evaluate the anti-tumor efficacy of the PTX-loaded hydrogel. IC1-R was found to have high sensitivity to pH/redox conditions, and the encapsulation rate can reach more than 98% at different PTX dosages. The structure of the IC1-R peptide was found to be a β-sheet under neutral conditions, which met the requirement for nanofiber network formation. Transmission electron microscopy and rheology tests confirmed that the suitable meshwork structure and improved mechanical and injectable properties of this hydrogel. In vitro and in vivo results showed that the blank hydrogel had good biological safety and confirmed the pH/redox sensitive properties of IC1-R-PTX, which allowed sustained delivery of the drug and enhanced tumor inhibition. In conclusion, this kind of PTX-loaded peptide hydrogel, which was formed in vitro, can be injected into tumors and can continuously and slowly release anti-tumor drugs under the stimulation of the tumor microenvironment to achieve the best anti-tumor effect and reduce toxicity and side effects. This biofunctional material has broad prospects in the field of drug delivery.