Li Liu
National Institutes of Health, USA
Title: Using an FDA approved nutrition supplement, intralipid, to improve delivery of anti-cancer nanodrugs: Effects on RES clearance and toxicity, EPR and immune modulation
Biography
Biography: Li Liu
Abstract
According to several meta-analysis studies, less than 1% of anti-cancer nanodrugs are delivered to target tumors. The reticuloendothelial system [(RES)/mononuclear phagocytic system (MPS)] is a key factor that affects nanodrug bio distribution and bioavailability by sequestering nanoparticles from the circulation (1). We have developed a method to temporarily blunt the RES by pre- administration of the FDA-approved nutritional supplement, Intralipid® (2-6). We have tested our Intralipid® method (2 g/kg, clinical dose) on the delivery of two different anti-cancer nanodrugs: (i) an experimental anti-cancer nanodrug, dichloro (1,2-diaminocyclohexane) platinum (II)-loaded and hyaluronic acid polymer-coated nanodrug (DACHPt/HANP) and (ii) the FDA-approved anti-cancer nanodrug, Abraxane®. We have found that pre-treatment with Intralipid® can reduce platinum accumulation in the liver, spleen, and kidney of rats by 20.4%, 42.5%, and 31.2%, respectively at 24-hr post DACHPt/HANP administration. Similarly, we have found in a xenograft breast cancer mouse model that pre-treatment with Intralipid® significantly increases the amount of Abraxane® that reaches tumors to promote tumor apoptosis and that the combination of Intralipid® with half the standard dose of Abraxane® can reduce tumor growth as effectively as the standard clinical dose. Intralipid® also promotes the polarization of macrophages to the anti-cancer M1-like phenotype. A recent study from Dr. Hiroshi Maeda and his colleagues showed a more important role of Intralipid® treatment, namely improving tumor blood flow, which is key for nanodrug delivery via the enhanced permeability and retention (EPR) effect (7). Thus, Intralipid® pre-treatment can be a new way to improve the delivery of anti-cancer nanodrugs with reduced off-target side effects and with improved drug efficacy. Our nanodrug delivery method is a general one, since it can apply to any existing nanodrugs as well as to those in development because there is no need to modify the drug and its nanocarrier.