Adsorptivemediated

Adsorptive-mediated endocytosis is a cellular uptake mechanism in which positively charged (cationic) extracellular cargo interacts with negatively charged components on the cell surface, such as glycosaminoglycans and proteoglycans, to trigger internalization. This process is non-specific compared to receptor-mediated endocytosis and can be exploited to enhance cellular delivery of proteins, nucleic acids, peptides, and nanoparticles that carry a net positive charge.

Mechanistically, initial adsorption to the cell surface occurs through electrostatic attraction, followed by membrane invagination and vesicle formation. Internalization can proceed via multiple routes, including clathrin- and caveolin-independent pathways and macropinocytosis. The process is energy-dependent and influenced by cargo charge, size, and concentration. Endosomal trafficking typically leads to acidification, which may affect cargo release or escape into the cytosol, depending on the design of the cargo or carrier.

In contrast to receptor-mediated endocytosis, adsorptive-mediated endocytosis lacks a single high-affinity receptor interaction and is therefore less selective and more dependent on physicochemical properties of the cargo. It can be rapid and broadly applicable, but it often results in non-specific uptake and can exhibit limited targeting. The approach is relevant in drug and gene delivery, particularly for cationic polymers, lipoplexes, and nanoparticles designed to enhance uptake across barriers or into difficult-to-target cells.

Limitations include potential cytotoxicity from cationic materials, variable efficiency across cell types, and nonspecific distribution. Design strategies commonly seek to balance positive surface charge with biocompatible coatings to mitigate toxicity while preserving uptake.

See also: endocytosis, receptor-mediated endocytosis, macropinocytosis, transcytosis.