Progress in lactoferrin-based nanocarriers for targeted cancer therapy

Lactoferrin (LF), an iron-binding glycoprotein, has recently emerged as a multifunctional potential nanocarrier for tumor-targeted drug delivery applications. Based on its ability to bind with high affinity to receptors overexpressed by cancer cells, LF enables receptor-mediated endocytosis and selective drug delivery to tumor tissues. A wide range of LF-based nanocarriers have been developed including LF nanoparticles (NPs), LF-drug nanoconjugates, LF-coated nanocarriers, LF-inorganic nanohybrids, LF nanogels, and LF-drug noncovalent nano-assemblies. These nanocarriers have shown improved tumor accumulation, enhanced antitumor efficacy, and decreased side effects in preclinical models of brain, prostate, breast, colorectal, and lung cancers. Although clinical translation is still in its early stages, recombinant human LF exhibited favorable pharmacokinetics and excellent safety profile in clinical trials. Future progress will require enhancing nanoparticle stability, limiting off-target biodistribution, and refining targeting strategies to account for heterogeneous receptor expression across tumors. Among promising future directions, engineering ultrasmall recombinant LF-based nanocarriers capable of penetrating dense tumor stroma holds potential applications in the treatment of desmoplastic tumors. Overall, LF-based nanocarriers offer a versatile platform for safe, receptor-mediated targeted cancer therapy.