title: Synthesis and characterization of pH-sensitive poly(itaconic acid)-poly(ethylene glycol)-folate-poly(l-histidine) micelles for enhancing tumor therapy and tunable drug release.
abstract: pH responsive intracellular tumor targeting is increasingly investigated as a pathway to trigger the release of anti-tumor drugs once the drug carrier reached the unique acidic environment of the solid tumors or after the drug carrier has been taken up by cells, resulting in the localization of the micelles in the acidic endosomes and lysosomes. Poly(itaconic acid)-poly(ethylene glycol)-folate-poly(l-histidine) (PIA-PEG-FA-PHIS) was synthesized as a carrier for tumor-targeted drug delivery. The micelles were internalized by receptor-mediated endocytosis, and the combination of active targeting and triggered release resulted in apparent cytotoxicity and antitumor activity. The MTT assay showed DOX-loaded micelles had higher and obvious cytotoxicity against Hela cells at pH 5.0 than that at pH 7.4. Cellular uptake experiments revealed that these pH-responsive PIA-PEG-FA-PHIS micelles were taken up in great amounts by receptor-mediated endocytosis and delivered to lysosomes, triggering release of DOX into the cytoplasm. These indicated that the PIA-PEG-FA-PHIS micelles could be a promising drug delivery system with preeminent stability for targeting the hydrophobic drugs to cancer cells and releasing DOX in to the cells by sensing the acidic environment of the endosomes for cancer therapy.
authors.affiliation: Alan G. MacDiarmid Institute of Jilin University, 2699 Qianjin Street, Changchun, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Alan G. MacDiarmid Institute of Jilin University, 2699 Qianjin Street, Changchun, China. Electronic address: maishilou134@163.com.
authors.forename: Yapeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Basic Medical, Jilin University, 261 Xinmin Street, Changchun 130023, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Nan
authors.affiliation: College of Basic Medical, Jilin University, 261 Xinmin Street, Changchun 130023, China.
authors.forename: Liangzi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Alan G. MacDiarmid Institute of Jilin University, 2699 Qianjin Street, Changchun, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Alan G. MacDiarmid Institute of Jilin University, 2699 Qianjin Street, Changchun, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D006367:HeLa Cells; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry*; D013386:Succinates / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D013386:Succinates; C552831:poly(ethylene glycol)-folate; C033223:polyhistidine; D011092:Polyethylene Glycols; D006639:Histidine; D005492:Folic Acid; C005229:itaconic acid
keywords: Doxorubicin; Drug delivery; Micelle; Poly(l-histidine); pH-responsive