Ligand-targeted particulate nanomedicines undergoing clinical evaluation: current status

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Nanomedicines are established in clinical practice, primarily relying on physicochemical properties for biodistribution.
• Ligand-targeted nanomedicines have shown preclinical success but lack clinical approval.
• Antibody-drug conjugates are an exception among approved nanomedicines.

Purpose of the Study:

• To review the clinical progress of ligand-targeted particulate nanomedicines (PNMs).
• To analyze the safety, efficacy, and role of targeting ligands in PNM performance.
• To identify future directions for ligand-targeted nanomedicine development.

Main Methods:

• Review of 13 ligand-targeted PNMs that entered clinical trials.
• Analysis of preclinical and clinical data for each PNM.
• Assessment of the contribution of targeting ligands to efficacy and biodistribution.

Main Results:

• Ligand-targeted PNMs are predominantly developed for cancer treatment.
• Preclinical data indicate safety and efficacy, but ligand contribution is not always clear.
• Targeting ligands enhance cellular internalization and retention, not initial localization.

Conclusions:

• Further understanding of in vivo behavior is crucial for clinical translation.
• Ligand-targeted PNMs offer potential for drug delivery across cell membranes and overcoming resistance.
• Future applications include targeting tumor vasculature and crossing the blood-brain barrier.