title: Photosensitizer enhanced disassembly of amphiphilic micelle for ROS-response targeted tumor therapy in vivo.
abstract: This study reports a reactive oxygen species (ROS) sensitive drug delivery system based on amphiphilic polymer of poly(propylene sulfide)-polyethylene glycol-serine-folic acid (PPS-mPEG-Ser-FA). The polymer could form homogeneous micelles with an average diameter of around 80 nm through self-assembly, which would then be loaded with the singlet oxygen-generating photosensitizer of zinc phthalocyanine (ZNPC) and anti-cancer drug of DOX. The disassembly of micelles could be triggered by the hydrophobic to hydrophilic transition of the PPS core in response to ROS-induced oxidation in vitro. ZNPC molecules are capable of producing ROS under laser irradiation, which results in the rapid disassembly of micelles and releasing of the anti-tumor drug for tumor therapy under physiological condition otherwise. Moreover, the excessive ROS production deriving from ZNPC synergically induces cells apoptosis. Furthermore, the DOX loaded amphiphilic micelles could be internalized by tumor cells via FA receptor-mediated endocytosis to effectively inhibit the tumor growth in vivo, while with only minimal toxic side effects. The results in vitro and in vivo consistently demonstrate that the light-responsive micelle is a promising biodegradable nanocarrier for on-command drug release and targeted tumor therapy.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Dai
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Menghuan
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Xinkun
authors.initials: X
authors.lastname: Shen
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Gu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, Chongqing 400044, PR China. Electronic address: kaiyong_cai@cqu.edu.cn.
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Cai
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage*; D004655:Emulsions / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry; D054833:Isoindoles; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000737:chemistry; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013501:Surface-Active Agents / Q000737:chemistry; D016896:Treatment Outcome; D017967:Zinc Compounds
chemical_list: D000903:Antibiotics, Antineoplastic; D004655:Emulsions; D007211:Indoles; D054833:Isoindoles; D008823:Micelles; D053769:Nanocapsules; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011108:Polymers; D017382:Reactive Oxygen Species; D013501:Surface-Active Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D004317:Doxorubicin
keywords: Disassembly; Photosensitizer; ROS-response; Self-assembly micelle; Targeted tumor therapy