Bioinspired peptosomes with programmed stimuli-responses for sequential drug release and high-performance anticancer...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Combination therapy offers enhanced efficacy for cancer treatment.
• Co-delivery systems are needed for sequential drug release, increasing intra-tumoral drug concentration and reducing side effects.

Purpose of the Study:

• To develop a peptosome (PS)-based co-delivery system for sequential release of a therapeutic peptide (Pe) and chemodrug (Curcumin/Cur).
• To design a system responsive to tumor microenvironments for targeted drug delivery and enhanced therapeutic outcomes.

Main Methods:

• Self-assembly of α-lactalbumin peptides into peptosomes (PS).
• Disulfide bond cross-linking of PS using endogenous thiol groups.
• Sequential drug release triggered by matrix metalloproteinases (MMP), pH, and glutathione (GSH) in the tumor microenvironment.

Main Results:

• The PePm/PS/Cur system demonstrated sequential release of Pe and Cur in response to tumor microenvironment stimuli.
• Enhanced internalization into tumor cells via a proton-sponge effect for lysosomal escape.
• Significant in vitro and in vivo antitumor and antimetastatic efficacy was observed.

Conclusions:

• The developed peptosome co-delivery system offers a promising strategy for sequential drug release in cancer therapy.
• This system exhibits enhanced therapeutic and antimetastatic effects with reduced side effects, highlighting its potential in clinical applications.