Background: Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery
Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing
to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor
therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the
tumor site in three ways: “passive”, “active”, and “smart” targeting.
Objective: To summarize the mechanisms of various internal and external “smart” stimulating factors on the basis
of findings from in vivo and in vitro studies.
Method: A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel
articles related to the subject.
Results: Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors
(temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), “smart” DDSs exhibit targeted
delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes.
Conclusion: In this review article, we summarize and classify the internal and external triggering mechanism of
“smart” nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated
for better understanding.