Endocytosis Pathway Self-Regulation for Precise Image-Guided Therapy through an Enzyme-Responsive Modular Peptide...

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Drug Delivery

Background:

• Lysosomal trapping of probes hinders intracellular delivery and therapeutic efficacy.
• Current methods for lysosomal escape do not prevent degradation by lysosomal hydrolases.

Purpose of the Study:

• To design an enzyme-responsive peptide probe (PKP) for enhanced mitochondrial delivery.
• To overcome lysosomal degradation and improve image-guided cancer therapy.

Main Methods:

• Designed a modular peptide probe (PKP) cleaved by matrix metalloproteinase-2 (MMP-2).
• Utilized Pal-part to induce a shift from clathrin-mediated endocytosis (CME) to caveolae-mediated endocytosis (CvME) for KP-part.
• Achieved direct mitochondrial delivery of KP-part, avoiding lysosomes.

Main Results:

• PKP effectively bypassed lysosomes by altering cellular uptake pathways.
• Mitochondrial delivery efficiency of KP-part was significantly improved.
• Demonstrated potential for delivering siRNA and doxorubicin for image-guided cancer therapy.

Conclusions:

• The PKP system offers a self-regulating intracellular delivery strategy for enhanced mitochondrial targeting.
• This approach optimizes image-guided therapeutic efficiency and holds promise for personalized cancer treatment.