Effect of ligand density and PEG modification on octreotide-targeted liposome via somatostatin receptor in vitro and in vivo

Octreotide had been exploited as a targeting ligand for nanoparticle tumor localization overexpressing somatostatin receptor. In addition to particle size and other physiochemical properties, ligand density had great influence on the delivery of active targeted nanoparticles. Herein, octreotide-targeted liposomal doxorubicin was constructed with different ligand density by post-inserting HSPE-PEG4000-Octreotide into pre-formed liposome. The octreotide ligand insertion was confirmed by activity detection of octreotide in HSPE-PEG4000-Octreotide with synchronous fluorescence. 1% octreotide density could achieve the best uptake efficiency on NCI-H-446 and SMMC-7721 cell lines among all liposomes. Octreotide-grafted long-circulating liposome (Oct-SSL) was prepared based on 1% octreotide density. The results showed that the insertion of PEG reduced cellular uptake and cytotoxicity. However, Oct-SSL showed a higher MRT compared with Oct-L showing the relative higher long circulating effect in pharmacokinetic study. Oct-SSL also showed tumor growth inhibition of twofold compared with other groups in Heps xenograft model mice. Oct-SSL with suitable ligand density and PEG modification exhibited significant effective tumor targeting for antitumor drug delivery.