(A) Cholesterol-sensitive macropinocytosis is the major pathway responsible for lipoplex internalization and is regulated by formation of large endocytic vesicles of irregular size and shape. (B) Once inside the cell, the complexes are actively transported from endosomes to lysosomes, preferentially, along the microtubules, near the MTOC for degradation. (C) Only a few of the DNA molecules can escape from endosomes to cytoplasm before entering lysosomes and even less will enter the nucleus for transcription.
MTOC: microtubule organizing center.