Limitations and niches of the active targeting approach for nanoparticle drug delivery

Abstract The active targeting approach has been widely employed to improve nanoparticle drug delivery. Contrary to popular conceptions, attachment of a targeting ligand to a nanopaticle does not alter its biodistribution, but only increases its internalization by target cells. Despite its potential, this strategy has drawbacks that can negate efficacy against tumors. Specifically, compared to non-targeted nanoparticles, a number of active targeting nanoparticles have decreased blood circulation time due to non-specific binding or immunogenicity, reduced tumor penetration, and high susceptibility to lysosomal degradation after internalization. In order to maximize the advantages and overcome the disadvantages, the active targeting approach is best suited for delivering membrane impermeable drugs to targets directly exposed to i.v. injected nanoparticles, such as those in circulation or in the luminal site of tumor vasculatures.