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Advances in the study of tumor pH-responsive polymeric micelles for Cancer drug targeting delivery

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Author:
No author available
Journal Title:
ACTA PHARMACEUTICA SINICA
Issue:
12
DOI:
10.3321/j.issn:0513-4870.2009.12.003
Key Word:
pH响应;聚合物;胶束;肿瘤;药物输送系统;纳米医学;化学治疗;pH-responsive;polymer;micelle;neoplasm;drug delivery system;nanomedicine;cheanotherapy

Abstract: This review presents the state of the an of pH-responsive polymeric micelles for cancer drug delivery.Solid tumors have a weakly acidic extracellular pH(pH<7),and cancer cells have even more acidic pH in endosomes and lysosomes(pH 4-6).The pH-gradients in tumor can be explored for tumor targeting and drug release in cancer drug delivery by applying pH-responsive polymeric micelles.The pH-responsive polymeric micelles consist of a corona and a core,and are made of amphiphilic copolymers,in which there are pH-responsive polymeric blocks.Two types of pH-responsive polymers-protonizable polymers and acid-labile polymers have been mainly used to make pH-responsive micelles for drug delivery.The protonizable polymers are polybases or polyacids,and their water-soluble/insoluble or charge states undergo changes with the protonation or deprotonation stimulated by external acidity,while the acid-labile polymers change their physical properties by chemical reaction stimulated by the acidity.Polymeric micelles whose core or coronas respond to the tumor extracellular acidity can be explored for triggering the fast release of the carried drug,activating the targeting group and accelerating the endocytosis of drug-loaded polymeric micelles,and those whose core or coronas respond to the tumor lysosomal acidity can be used for facilitating their escape from the lysosomes and targeting the nucleus.Various in vivo and in vitro experiments demonstrated that pH-responsive polymeric micelles are effective for cellular targeting,internalization,fast drug release and nuclear localization,and hence enhancing the therapeutic efficacy and reducing the side effect of cancer chemical therapy.

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