In vitro and in vivo evaluation of APRPG-modified angiogenic vessel targeting micelles for anticancer therapy

The study was aimed to evaluate the antitumor potential of the Ala-Pro-Arg-Pro-Gly (APRPG)-modified angiogenic vessel targeting drug delivery system using paclitaxel (PTX) as a model drug. In this study, an angiogenesis homing peptide APRPG was conjugated to the amphipathic copolymer PLGA–PEG and the synthesized copolymer APRPG–PEG–PLGA was used to prepare PTX encapsulated micelles (APRPG–PEG-Mic). The micelles were uniform spherical and exhibited a unimodal particle size distribution and a slight negative zeta-potential. The in vitro drug release result demonstrated a significant sustained release property of APRPG–PEG-Mic. Compared to Taxol® and Cont-PEG-Mic, APRPG–PEG-Mic showed a stronger cytotoxicity against two cancerous cell lines. In the cell uptake studies, the APRPG-modified micelles enhanced intracellular fluorescent intensity in EA.hy926 cells. The biodistribution study revealed the accumulation of APRPG–PEG-Mic in tumor tissues as a result of passive accumulation and active targeting. In comparison with Taxol® and Cont-PEG-Mic, APRPG–PEG-Mic reduced the tumor volume more significantly and prolonged the survival time of tumor-bearing mice, indicating a higher antitumor efficacy and lower systematic side effects of APRPG–PEG-Mic. The results indicated that APRPG-modified micelles could be an efficient target-delivery method to angiogenic vessels and a highly promising therapeutic system in anticancer therapy.