Preparation and In Vitro and In Vivo Antitumor Effects of VEGF Targeting Micelles.

BACKGROUND

Doxorubicin (DOX) has antitumor effects mediated by cell viability inhibition and by inducing cellular apoptosis. However, it has limited use in clinical applications due to various factors such as hydrophobicity, dose-dependent toxicity effects on normal tissues, short cycle retention time, and low targeting ability. This study aims at enhancing hydrophilicity of DOX to restrict its toxic effects to within or around the tumor sites and also to improve its targeting ability to enhance antitumor efficiency.

METHODS

Micelles composed of biodegradable poly (ethylene glycol)-poly (lactic acid) copolymers (PEG-PLA) were employed to deliver DOX via a self-assembly method and were coupled to VEGF antibodies. The morphology, size, and physical stability of PEG-PLA-DOX targeting VEGF micelles (VEGF-PEG-PLA-DOX micelles) were assessed. Then, the release ability of DOX from these micelles was monitored, and their drug loading capacity was calculated. MTT assay revealed the antitumor effect of VEGF-PEG-PLA-DOX micelles. Moreover, ROS release was measured to evaluate apoptotic effects of these nanoparticle micelles. therapeutic efficiencies of VEGF-PEG-PLA-DOX micelles on a lung cancer nude mouse model was evaluated.

RESULTS

DOX-loaded micelles were obtained with a drug loading capacity of 12.2% and were monodisperse with 220 nm average diameter and a controlled DOX release for extended periods. In addition, VEGF-PEG-PLA-DOX micelles displayed a larger cell viability inhibitory effect as measured via MTT assays and greater cell apoptosis induction through ROS levels compared with PEG-PLA-DOX micelles or free DOX. Furthermore, VEGF-PEG-PLA-DOX micelles could improve antitumor effects of DOX by reducing tumor volume and weight.

CONCLUSIONS

VEGF-PEG-PLA-DOX micelles displayed a larger anti-tumor effect both in A549 cells and in an lung cancer nude mouse model compared with PEG-PLA-DOX micelles or free DOX, and hence they have potential clinical applications in human lung cancer therapy.