Synthesis And Study Of MPEG-Poly (β-amino Ester)s Amphiphilic Block Copolymers

How to construct a drug delivery system that is safe, efficient and responsive totumor microenvironment still remains a key issue for cancer therapy. In this study,amphiphilic block copolymers were synthesized by using mPEG and Poly(β-aminoester), which has pH and reduction sensitive groups in the backbone, so it can respondrapidly to the stimuli of tumor microenvironment and achieve smart drug delivery.The specific contents are as follows:1) Synthesis and characterizations of mPEG-PAEs block copolymers. FourmPEG-PAEs with tunable molecular weight and constitution were obtained throughMichael-addition reaction, the hydrophilic/hydrophobic ratio and disulfide contentwas controlled by changing monomer feed ratios, the detailed structure and molecularweight of mPEG-PAEs were characterized by using1H-NMR and GPC.2) Self-assembly of mPEG-PAEs and investigation of its pH/reduction dual-sensitivity. Micelles or polymersomes were obtain from these amphiphilic copolymersthrough self-assembly, whose sizes ranged from176.1~197.1nm with uniformdistribution, and CAC ranged from0.012~0.019mg/ml in water; the pH and reductiondual-sensitivity of mPEG-PAEs was revealed in detail by using acid-base titration,1H-NMR and DLS.3) In vitro drug release of DOX-loaded nanoparticles. Doxorubicin was loadedinto mPEG-PAEs aggregates with a decent drug loading content, and then in vitroDOX release was conducted in acid/reductive environment, the results showed thatdrug release was significantly accelerated in acidic pH or high reducing conditions,further testifying the effectiveness of its dual-sensitivity for smart drug release.4) Cytotoxicity and cellular uptake of mPEG-PAEs aggregates towards Helacells. MTT assay showed little cytotoxicity of mPEG-PAEs with80%cell viability at0.5mg/ml, cellular uptake of DOX-loaded mPEG-PAEs by fluorescence microscopyconfirmed it can successfully deliver and release DOX into cytosol of Hela cells.The abovementioned investigation has fully demonstrated the pH and reductiondual-sensitivity of mPEG-PAEs block copolymers, so this kind of polymer showsgreat potential for smart drug delivery in the cancer treatment.