Preparation And Characterization Of TRAIL-modified,Cabazitaxel-Loaded Polymeric Micelles

In the treatment of cancer,the combination of two or more drugs has received widespread attention.Cabazitaxel(CTX)is a taxoid drug,which strengthens the tubulin polymerization and inhibits cell mitosis and interphase cell function.However,its efficacy and safety are afFected due to the toxic side effects of its delivery excipients in commercial formulations and its poor water solubility,the use of micellar drug delivery can improve the water solubility and targeting of drugs.However,different caneer eells have different EPR effect of micelles,and CTX is not effective for all cancer cells.To improve the targeting of CTX-loaded micelles and enhance their inhibitory effect on cancer cells,in this subject,I synthesized the TRAIL-modified,cabazitaxel-loaded polymeric micelles(TRAIL-M-CTX),and the main results are as follows:1)Firstly,the biodegradable block polymer molecule poly(ethylene glycol)-b-poly(DL-lactide)(mPEG-PLA)was synthesized by the ring-opening polymerization method.The molecular weight of the polymer mPEG2000-PLA1889 was detected by nuclear magnetic resonance spectroscopy.Then the critical micelle concentration(CMC)of the micelles formed by the polymer was detected by fluorene fluorescent probe method.The CMC was 0.069 mg/ml,indicating that the prepared mPEG2000-PLA1889 can form thermodynamically stable micelles at lower concentrations.2)We prepared TRAIL-modified and CTX-loaded polymer micelle(TRAIL-M-CTX).This nanoparticle was self-assembled from amphiphilic copolymers mPEG-PLA,COOH-PEG-PLA(purchased),and CTX by nanoprecipitation method to form uncoupled micelles,and then conjugated with TRAIL protein to modify the surface of micelles.The prepared TRAIL-M-CTX particle size was 39.75±0.17nm,and the drug entrapment efficiency was 95.52±1.69%.The proton coupling between protein and micelles was confirmed by nuclear magnetic resonance spectroscopy,Fourier transform infrared spectroscopy and dynamic laser scattering.3)Two human cancer cell lines(NCI-H460 and MCF-7)with different TRAIL sensitivities were selected.In vitro activity analysis showed that TRAIL-M-CTX has higher antitumor activity than TRAIL protein and CTX.Synergistic effects of TRAIL and CTX components on MCF-7 cells are shown in TRAIL-M-CTX micelles.A study of cellular drug uptake implied that the TRAIL protein modified micelles were internalized into MCF-7 cells more effectively than unmodified micelles,owing to the coupled TRAIL protein.The cell cycle assay of MCF-7 cells revealed that TRAIL-M-CTX caused a significant increase in the sub-G1 population,thus facilitating the apoptosis of cancer cells.