title: Self-Assembly of Porphyrin-Paclitaxel Conjugates Into Nanomedicines: Enhanced Cytotoxicity due to Endosomal Escape.
abstract: Nanomedicines assembled directly from drug molecules possess several advantages, including precise molecular structure and high content of drugs. Herein, porphyrin-paclitaxel conjugates (Py-s-s-PTX) were synthesized by using a disulfide bond as a linker. The Py-s-s-PTX could self-assemble into nanoparticles (Py-s-s-PTX NPs) with a size of about 100 nm via disulfide-induced assembly. Py-s-s-PTX NPs are highly stable under biological conditions and could be destroyed in the presence of reducing agents as revealed by dynamic light scattering. The obtained Py-s-s-PTX NPs could be internalized by cancer cells via endocytosis and disassociated in the reducing cytoplasm, thus releasing PTX in cancer cells. Endosomal escape triggered upon irradiation could enhance the cytotoxicity of paclitaxel, and Py-s-s-PTX NPs possess cytotoxicity comparable to that of free PTX. We believe that this disulfide-assembled nanomedicine represents a new and important development for chemotherapy in cancer therapy.
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Chemistry, Northeast Normal University, 5628 Renmin Street, Changchun, 130024, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China. xiez@ciac.ac.cn.
authors.forename: Zhigang
authors.identifier: http://orcid.org/0000-0003-2974-1825
authors.initials: Z
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011166:Porphyrins; D017239:Paclitaxel
keywords: conjugates; nanomedicines; paclitaxel; porphyrin; self-assembly