Discussion
mPEG-b-P(C7-co-CA) micelles can achieve osteosarcoma targeting effectively and enhance the anti-osteosarcoma effect of cinnamaldehyde in vitro. This research provides a promising drug delivery system for clinical application and tumor treatment.
Methods
First, an amphiphilic cinnamaldehyde polymeric prodrug [mPEG-b-P(C7-co-CA)] was synthesized through Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) polymerization and post-modification, and self-assembled into mPEG-b-P(C7-co-CA) micelles in an aqueous solution. The physical properties of mPEG-b-P(C7-co-CA) micelles, such as critical micelle concentration (CMC), size, appearance, and Zeta potential were characterized. The CA release curve of mPEG-b-P(C7-co-CA) micelles at pH 7.4, 6.5 and 4.0 was studied by dialysis method, then the targeting ability of mPEG-b-P(C7-co-CA) micelles to osteosarcoma 143B cells in acidic environment (pH 6.5) was explored by cellular uptakeassay. The antitumor effect of mPEG-b-P(C7-co-CA) micelles on 143B cells in vitro was studied by MTT method, and the level of reactive oxygen species (ROS) in 143B cells after mPEG-b-P(C7-co-CA) micelles treatment was detected. Finally, the effects of mPEG-b-P(C7-co-CA) micelles on the apoptosis of 143B cells were detected by flow cytometry and TUNEL assay.
Results
An amphiphilic cinnamaldehyde polymeric prodrug [mPEG-b-P(C7-co-CA)] was successfully synthesized and self-assembled into spheric micelles with a diameter of 227 nm. The CMC value of mPEG-b-P(C7-co-CA) micelles was 25.2 mg/L, and it showed a pH dependent release behavior of CA. mPEG-b-P(C7-co-CA) micelles can achieve chargeconversion from a neutral to a positive charge with decreasing pHs. This charge-conversion property allows mPEG-b-P(C7-co-CA) micelles to achieve 143B cell targeting at pH 6.5. In addition, mPEG-b-P(C7-co-CA) micelles present high antitumor efficacy and intracellular ROS generation at pH 6.5 which can induce 143B cell apoptosis.