title: Redox- and light-responsive alginate nanoparticles as effective drug carriers for combinational anticancer therapy.
abstract: Nanoparticles have been extensively explored as effective means to deliver chemotherapeutic agents or photosensitizers for chemotherapy or photodynamic therapy (PDT) against cancer. In the present work, pheophorbide A (PheoA), a hydrophobic photosensitizer, was conjugated via a redox-sensitive disulfide linkage to alginate (PheoA-ALG). Anticancer agent, doxorubicin (DOX), was also loaded within the PheoA-ALG nanoparticles (DOX/PheoA-ALG NPs) and used as drug carriers for combinational antitumor treatment. The DOX/PheoA-ALG NPs were spherical in shape with a uniform diameter of approximately 210 nm. Redox-responsive drug releasing properties were shown by the DOX/PheoA-ALG NPs, with an accelerated amount of DOX and PheoA release observed in the presence of a high glutathione level (10 mM). Cellular uptake results showed that DOX/PheoA-ALG NPs were readily taken up by B16 tumor cells (murine melanoma) and enhanced DOX and PheoA uptake were detectable in the DOX/PheoA-ALG NPs-treated B16 cells in comparison to carrier free drugs. DOX/PheoA-ALG NPs also elicited intracellular ROS generation, which leads to enhanced toxicity in B16 cells. In vivo studies using B16 tumor-bearing mice further demonstrated that DOX/PheoA-ALG NPs were preferentially accumulated in tumor tissues, resulting in substantial inhibition of B16 tumor growth by chemotherapy and photodynamic therapy, which is also attributable to DOX/PheoA-ALG NP-elicited increase of serum INF-λ levels. Our results demonstrate a major potential of DOX/PheoA-ALG NPs for combinational cancer therapy.
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. plumlichen@163.com.
authors.forename: Chuangnian
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. plumlichen@163.com.
authors.forename: Gaona
authors.initials: G
authors.lastname: Shi
authors.affiliation: Basic Nursing T&R Section, School of Nursing, Qingdao University, Qingdao, Shandong Province 26000, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Niu
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. plumlichen@163.com.
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. plumlichen@163.com.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. plumlichen@163.com.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. plumlichen@163.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China. plumlichen@163.com and Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071, China. Kongdeling@nankai.edu.cn.
authors.forename: Deling
authors.identifier: http://orcid.org/0000-0002-2961-9267
authors.initials: D
authors.lastname: Kong
mesh_terms: D000464:Alginates; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry* / Q000528:radiation effects; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D008027:Light; D008546:Melanoma, Experimental; D051379:Mice; D053758:Nanoparticles; D010084:Oxidation-Reduction; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage
chemical_list: D000464:Alginates; D000970:Antineoplastic Agents; D004337:Drug Carriers; D006603:Hexuronic Acids; D017319:Photosensitizing Agents; D004317:Doxorubicin; D020723:Glucuronic Acid