Chemotherapy through Lysosomes with a DNA-Daunorubicin Complex

Abstract

WHEN a drug can pass freely across cell membranes, it becomes distributed throughout the body fluids whichever its route of administration, and invades all cells by diffusion at comparable rates. But if it is firmly associated with a non-permeant, pino-cytizable and digestible carrier, it will tend to remain confined within a smaller fluid space determined by its route of administration, its excretion will be slow, and its intracellular penetration will be restricted to the endocytic route (Fig. 1). Free drug will then appear first within lysosomes, following digestion of the carrier. From the lysosomes it will diffuse into the other parts of the cells, and eventually into the extracellular fluids. The intracellular concentration of the drug thus becomes dependent on the pinocytic activity of the cells and on the digestive potential of their lysosomes, and must exceed the extracellular concentration in the most active cells. Obviously, this model requires the complex to be stable in the body fluids, and to dissociate inside lysosomes. The drug itself must be resistant to lysosomal inactivation.