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  • Title: pH-triggered intracellular release from actively targeting polymer micelles.
    Author: Guo X, Shi C, Wang J, Di S, Zhou S.
    Journal: Biomaterials; 2013 Jun; 34(18):4544-54. PubMed ID: 23510854.
    Abstract:
    Chemotherapy is widely applied to treat cancer patients but its application is limited due to the systemic toxicity and low efficacy. Nanocarrier system, which is capable of delivering their toxic cargos specifically into cancer cells and then greatly overcomes these disadvantages, has drawn a broad attention. Here we developed a drug-conjugated micelle for a better drug delivery in which folic acid was attached to the DOX-conjugated poly(ethylene glycol)-poly(ε-caprolactone) to target tumor; DOX was further connected with a hydrazone linker (FA-hyd) for a pH-triggered drug release. Comparing to other DOX-conjugated micelles either linked with carbamate (FA-cbm) or lacking FA(m-hyd), the developed FA-hyd demonstrated excellent biocompatibility; When analyzed with Alamar blue assays, flow cytometry and confocal laser scanning microscopy (CLSM), the pH-sensitive FA-functionalized DOX-conjugated micelles presented much better efficiency of cellular uptake and higher cytotoxicity to tumor cells. In vivo pharmacokinetics and biodistribution studies indicated that FA-hyd micelles significantly prolonged the blood circulation time of drug and enriched drug into the tumors rather than normal tissues. In vivo antitumor activity demonstrated that FA-hyd micelles had the highest safety to body and the best therapeutic efficacy to tumors. Therefore, this drug delivery system is deemed as a potential nanocarrier for cancer therapy.
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