Acid active receptor-specific peptide ligand for in vivo tumor-targeted delivery

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Oncology

Background:

• Effective cancer therapy requires precise targeting of tumor cells, especially in early stages.
• Current receptor-mediated drug delivery systems face challenges due to off-target accumulation in normal tissues, causing adverse effects.
• Tumor microenvironment characteristics, like acidosis, offer a potential target for selective drug release.

Purpose of the Study:

• To develop a tumor-targeting drug delivery system that leverages the acidic tumor microenvironment for selective activation.
• To design a system that minimizes off-target accumulation and enhances therapeutic efficacy.
• To investigate the potential of pH-sensitive linkages in receptor-specific ligands for cancer treatment.

Main Methods:

• Conjugation of a shielding molecule to a receptor-specific ligand using a pH-sensitive hydrazone bond.
• Utilizing the acidic extracellular pH of tumors to trigger the detachment of the shielding molecule.
• Evaluating the enhanced tumor-to-background accumulation ratio of the modified delivery system.

Main Results:

• Demonstrated acid-activated detachment of the shielding molecule in the tumor microenvironment.
• Achieved an enhanced tumor/background accumulation ratio compared to conventional methods.
• Validated the principle of using pH differences to control receptor-mediated endocytosis.

Conclusions:

• Acid-active receptor-specific peptide ligand-modified delivery systems show promise for targeted cancer therapy.
• Exploiting tumor acidosis offers a strategy to improve drug delivery specificity and reduce systemic toxicity.
• This approach has potential applications in the early-stage treatment of various solid tumors.