title: Inspired by nonenveloped viruses escaping from endo-lysosomes: a pH-sensitive polyurethane micelle for effective intracellular trafficking.
abstract: A multifunctional drug delivery system (DDS) for cancer therapy still faces great challenges due to multiple physiological barriers encountered in vivo. To increase the efficacy of current cancer treatment a new anticancer DDS mimicking the response of nonenveloped viruses, triggered by acidic pH to escape endo-lysosomes, is developed. Such a smart DDS is self-assembled from biodegradable pH-sensitive polyurethane containing hydrazone bonds in the backbone, named pHPM. The pHPM exhibits excellent micellization characteristics and high loading capacity for hydrophobic chemotherapeutic drugs. The responses of the pHPM in acidic media, undergoing charge conversion and hydrophobic core exposure, resulting from the detachment of the hydrophilic polyethylene glycol (PEG) shell, are similar to the behavior of a nonenveloped virus when trapped in acidic endo-lysosomes. Moreover, the degradation mechanism was verified by gel permeation chromatography (GPC). The endo-lysosomal membrane rupture induced by these transformed micelles is clearly observed by transmission electron microscopy. Consequently, excellent antitumor activity is confirmed both in vitro and in vivo. The results verify that the pHPM could be a promising new drug delivery tool for the treatment of cancer and other diseases.
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. jiehua_li@scu.edu.cn hongtan@scu.edu.cn.
authors.forename: Nijia
authors.initials: N
authors.lastname: Song
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. jiehua_li@scu.edu.cn hongtan@scu.edu.cn.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. jiehua_li@scu.edu.cn hongtan@scu.edu.cn.
authors.forename: Jiehua
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. jiehua_li@scu.edu.cn hongtan@scu.edu.cn.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Pan
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. jiehua_li@scu.edu.cn hongtan@scu.edu.cn and Laboratory Animal Center of Sichuan University, Huaxi Clinical College, Sichuan University, Chengdu, 610040, China.
authors.forename: Xueling
authors.initials: X
authors.lastname: He
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. jiehua_li@scu.edu.cn hongtan@scu.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Tan
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. jiehua_li@scu.edu.cn hongtan@scu.edu.cn.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Wan
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. jiehua_li@scu.edu.cn hongtan@scu.edu.cn.
authors.forename: Jianshu
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. jiehua_li@scu.edu.cn hongtan@scu.edu.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Ran
authors.affiliation: College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China. jiehua_li@scu.edu.cn hongtan@scu.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D063566:Biodegradable Plastics / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011140:Polyurethanes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014780:Viruses
chemical_list: D000970:Antineoplastic Agents; D063566:Biodegradable Plastics; D011140:Polyurethanes; D011092:Polyethylene Glycols; C000595209:polyethylene glycol 1000