Amphiphilic Hybrid Dendritic-Linear Molecules as Nanocarriers for Shape-Dependent Antitumor Drug Delivery

Nanoparticles based on hybrid block copolymers had been expected as effective nanocarriers for hydrophobic drug delivery. Herein, the novel dendritic-linear molecules from OEG dendron conjugated with octadecylamine (G2-C18) was designed, synthesized, and further applied as nanocarrier to prepare 10-hydroxycamptothecin (HCPT) nanoparticles via antisolvent precipitation method. It seemed that the feed weight ratio of HCPT vs G2-C18 not only affected the drug-loading content of nanoparticles but also influenced the morphology of HCPT nanoparticles; the morphology of HCPT nanoparticles was changed from nanosphere (NSs) to nanorod (NRs) with increasing the feed weight ratio. Both of HCPT nanoparticles presented good stability and similar drug release profiles, but different anticancer efficacy and cellular uptake mechanism. The cytotoxicity of HCPT NRs was enhanced significant comparing with HCPT NSs, the IC₅₀ value was 2-fold lower than HCPT NSs ( p < 0.05). More importantly, HCPT NRs showed apparently higher antitumor activity in vivo, the inhibition rate of HCPT NRs was 1.3-fold higher than HCPT NSs. Based on these results, it suggested that the antitumor activity could be influenced significantly by particle morphology, which should be considered and optimized during the nanocarrier design.