Behavior and anti-glioma effect of lapatinib-incorporated lipoprotein-like nanoparticles

The purpose of the investigation was to prepare a new type of nanoparticle, namely lapatinib-incorporated lipoprotein-like nanoparticles (LTNPs), and to evaluate the behavior and anti-glioma effect of LTNPs. LTNPs were prepared and characterized using the Cyro-transmission electron microscope (Cryo-TEM) and Raman scan methods. Cellular uptake and subcellular localization studies were performed to evaluate the in vitro behavior of LTNPs. An in vivo imaging technique was used for the evaluation of the targeting of LTNPs. To study the anti-glioma effect, glioma xenografts were used. The particle size of LTNPs was 92.6 nm, and the zeta potential was 28.40 mV. LTNPs contained a surface layer that was obviously different from the core, according to the Cryo-TEM analysis. A Raman scan analysis demonstrated the incorporation of lapatinib in LTNPs, and it also revealed a structure different from free lapatinib. The uptake of LTNP by U87 cells occurred in a concentration- and time-dependent manner. According to the subcellular study, the uptake of LTNPs was endosome mediated. LTNPs could distribute and accumulate in the tumor site by an enhanced permeation and retention effect. Both LTNPs (10 mg kg−1) and LTNPs (30 mg kg−1) could significantly inhibit the growth of U87 xenografts. For a similar antitumor effect, the required cumulative dose of LTNPs was only 5% compared to that of Tykerb (the commercial formulation of lapatinib). This study demonstrated the effective uptake of LTNPs by U87 cells, the passive targeting of LTNPs at tumors and the better antitumor effect of LTNPs.