| Among the various drug delivery systems, amphiphilic copolymer micelles with core-shell structure have gained increasing attention due to their enhancement of drug delivery efficiency, improvement of hydrophobic drug solubility, and minimization of drug side effects. But the micelles have low stability since large volume dilution and interactions with blood after i.v. injection, which often leads to micelle dissociation or aggregation, premature leakage of drug and low bioavailability. So we design a stimuli-responsive cross-linked micelles (SCMs) with active targeted.Firstly, we developed a redox-responsive and photo-crosslinked micellar system by simply mixing photo-initiated cross-linking amphiphilic copolymer 6arm PEG-PCCL with phenylboronic acid (PBA) functionalized redox-sensitive amphiphic copolymer PBA-PEG-ss-PCL. By UV 365 nm light irradiation, the core crosslink micelle were obtained. The properties of materials and micelles were demonstrated by 1HNMR, GPC, DLS and TEM evaluation.Secondly, we prepared DOX-loaded micelles, which were used for in vitro drug release study in a stimulated physiological environment. We found that the DOX release was influenced by crosslink degree and disulfide bonds, and DOX@PBA-ss-CLM-20min (1:1, w/w) was chosen to the experiment group for its appropriate drug release rate. In vitro results demonstrates that the micelles have good biocompatibility, and the DOX-loaded micelles can inhibit the growth of cancer cells due to that the micelles can be specifically internalized into tumor cells via PBA-mediated endocytosis and then the encapsulated DOX is promptly released in cytoplasm in response to a high level of GSH.Lastly, The in vivo antitumor effect on H22 bearing BALB/c mice displayed that the DOX@PBA-ss-CLM-20min possessed the best therapeutic efficacy due to the smallest tumor volume and weight on day 21st and the slowest increase rate of tumor, as well as the biggest degree of apoptosis obtained from the histological assessments. |
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