The present disclosure relates to the design and use of specific drug-nanoparticle constructs where the loading of the drugs onto nanoparticle are through noncovalent interactions. The obtained nanoconstructs are smaller than 10 nm in hydrodynamic diameter in the physiological environment, are highly resistant to serum protein adsorption, can penetrate the tumor core deeply via passive diffusion, can be retained in the tumor cores through enhancement permeability and retention effect, can rapidly diffuse across interendothelial junctions but can also be rapidly eliminated from the background tissues and normal organs. In addition, “off-target” drug-particle nanoconstructs have very low accumulation in the liver and can be eliminated through the urinary system. Through the use of these nanoparticles, the toxicity and side effect of chemodrugs is significantly reduced and the therapeutic index greatly improved.
