Ligand-modified Lipid-based Drug Delivery Vehicles for the Selective Targeting of Cancerous Cells

Chemotherapy is widely recognized as the mainstay of cancer therapy; however, its lack of specificity and off-target toxicities limit therapeutic success. The lipid-based nanocarriers with targeting ligands such as folic acid, transferrin, aptamers, and antibodies are widely recognized as effective for cancer cell targeting. However, no ligand-modified lipid-based system has reached regulatory approval despite three decades of preclinical development. This review synthesizes and evaluates mechanistic, computational, and translational aspects of ligand-modified lipid nanocarriers. The review discusses lipid drug delivery systems in cancer and targeting strategies, mainly focusing on active targeting by ligands. The ligands are compared against standardized criteria, revealing no single class dominates but rather a balance of competing properties. The enhanced permeability and retention (EPR) effect is examined against clinical evidence. The barriers for ligand-modified lipid-based nanoparticles that can affect the ligand targeting efficiency are discussed. Given the redirected accumulation of LNPs in the liver, which leads to hepatic tropism, approaches such as biomimetics and stealth ligand modification are discussed as strategies to prolong circulation and improve therapeutic efficacy. Furthermore, applications of artificial intelligence to ligand-modified lipid nanoparticles are reviewed, with identification of gaps in application in ligand-modified LNPs. Clinically, FDA- and EMA-approved lipid formulations validate translational feasibility, though ligand-modified systems remain challenging due to manufacturing complexity and regulatory hurdles. This review uniquely integrates mechanistic, translational, and computational perspectives of ligand-modified lipid-based nanoparticle systems to bridge laboratory and preclinical innovation with clinical feasibility in cancer therapeutics.

Abstract from PubMed (PMID 43021032). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.