Title:Glimpse into the Cellular Internalization and Intracellular Trafficking of Lipid-
Based Nanoparticles in Cancer Cells
Volume: 22
Issue: 10
Author(s): Elham Kamal Kazemi, Fereydoon Abedi-Gaballu, Tala Farid Mohammad Hosseini, Ali Mohammadi, Behzad Mansoori, Gholamreza Dehghan*, Behzad Baradaran*Nader Sheibani
Affiliation:
- Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Keywords:
Cancer, cellular uptake, drug delivery, endocytosis, intracellular trafficking, lipid-based nanoparticles.
Abstract: Lipid-based nanoparticles, as drug delivery carriers, are commonly used for the delivery of anti-cancer therapeutic
agents. Due to their smaller particle size and similarity to cell membranes, Lipid-based nanoparticles are readily
internalized into cancer cells. Cancer cells also overexpress receptors for specific ligands, including folic acid, hyaluronic
acid, and transferrin, on their surface, thus, allowing the use of their ligands for surface modification of the
lipid-based nanoparticles for their specific recognition by receptors on cancer cells. This would also allow the gradual
intracellular accumulation of the targeted functionalized nanoplatforms. These ligand-receptor interactions eventually
enhance the internalization of desired drugs by increasing the nanoplatforms cellular uptake. The cellular internalization
of the nanoplatforms varies and depends on their physicochemical properties, including particle size, zeta potential,
and shape. The cellular uptake is also influenced by the types of ligand internalization pathways utilized by cells,
such as phagocytosis, macropinocytosis, and multiple endocytosis pathways. This review classifies and discusses lipidbased
nanoparticles engineered to carry specific ligands, their recognition by receptors on cancer cells, and their cellular
internalization pathways. Moreover, the intracellular fate of nanoparticles decorated with specific ligands and their
best internalization pathway (caveolae-mediated endocytosis) for safe cargo delivery are also discussed.