Cellular uptake and transport mechanism of lycopene-loaded nanomicelles formed by amphiphilic peptide self-assembly in the intestinal epithelium

J Sci Food Agric. 2025 Jan 24. doi: 10.1002/jsfa.14151. Online ahead of print.

Abstract

Background: This study aimed to elucidate the transport mechanism of lycopene-loaded nanomicelles to improve intestinal absorption of lycopene. The interactive mechanism between lycopene and nanomicelles was investigated through isothermal titration calorimetry (ITC). The cytotoxicity, cellular uptake, endocytosis, and intracellular transport pathways of lycopene-loaded nanomicelles were investigated using the Caco-2 cell model.

Results: The ITC results demonstrated that nanomicelles/lycopene binding was an entropy-driven spontaneous exothermic reaction, and hydrophobic interactions were the main driving force. Lycopene-loaded nanomicelles were not cytotoxic, and uptake of lycopene by Caco-2 cells increased 2.20-fold after nanoencapsulation. The results of intracellular transport of lycopene-loaded nanomicelles indicated that the endoplasmic reticulum, Golgi apparatus, and lysosomes play key roles in this process. The intracellular transport results showed that the endoplasmic reticulum, Golgi apparatus, and lysosomes were important organelles for intracellular transport of lycopene-loaded nanomicelles.

Conclusion: Nanomicelles effectively enhance the cellular uptake of lycopene and are promising carriers for its delivery. This study contributes to the understanding of the transport mechanism of nanomicelles through intestinal epithelial cells. © 2025 Society of Chemical Industry.

Keywords: Caco‐2 cells; intestinal uptake; intracellular transport; lycopene; nanomicelles.