Macropinocytosis Route for Drug Delivery: An Unexplored Avenue with Prospects and Challenges

Various approaches have been used to deliver therapeutic molecules (small and macro-molecules) into the cytosol, such as physical delivery (electroporation, microinjection), nanocarriers (lipid-based, inorganic, polymeric nanocarriers, virus-like carriers), fusion of antibody with autoantibodies (3E10, 5C6), cell fusion peptides etc. Most of these approaches relies on Clathrin-mediated endocytosis route for cellular uptake. Till date, Clathrin-mediated endocytosis is the most widely studied route in drug delivery. However, the macropinocytosis route has not been explored much for the purpose of drug delivery. To further expand the current landscape of drug delivery routes, we attempted to explore macropinocytotic route for the delivery of therapeutic molecules with aid of macropinocytosis inducers. Our preliminary data has demonstrated feasibility of using macropinocytosis inducers to facilitate uptake of both large and small molecules into the cells. Based on our observations, further optimization of macropinocytosis inducers could facilitate uptake of wide range of therapeutic molecules for intracellular targeting.