title: A hematoporphyrin-based delivery system for drug resistance reversal and tumor ablation.
abstract: Nanotechnology-based drug delivery systems have been intensively investigated, while only a few of them can be used for clinic application. Hematoporphyrin (HP), a major molecule in erythrocyte, has been widely used in photodynamic therapy (PDT). In the present study, polyethylene glycol (PEG) modified hematoporphyrin (HPP)-based nanoparticle system was designed to load doxorubicin (HPPD), in achieving a synergistic effect of chemotherapy and PDT. Herein we presented that HPPD formed narrowly dispersed nanoparticles at 35 ± 2 nm, yielding an enhanced drug release at pH5.8 along with laser radiation. This combined treatment with HPPD and radiation facilitated drug penetration to the nucleus thereby reducing 12-fold decrease in IC50 value and promoting apoptosis in drug-resistant breast cancer cells. Notably, little toxicity was detected with HPP at the cellular level and in animal models. Live animal imaging revealed that HPPD performed ultra high tumor uptake in both mice and marmoset models. Strikingly, intravenous administration of HPPD and radiation on the tumor achieved efficient tumor ablation, without inducing myocardial injury. We report here the development of a biomolecule, HP-based nanoparticle system, which can synergistically yield chemotherapy and PDT.
authors.affiliation: Research Center of Basic Medical Sciences & Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Research Center of Basic Medical Sciences & Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Research Center of Basic Medical Sciences & Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Research Center of Basic Medical Sciences & Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Head & Neck, Tianjin Cancer Institute and Hospital, Tianjin 300060, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China.
authors.forename: Xubo
authors.initials: X
authors.lastname: Yuan
authors.affiliation: School of Materials Science and Engineering, Tianjin University, Tianjin 300072, PR China.
authors.forename: Chaoyong
authors.initials: C
authors.lastname: Liu
authors.affiliation: School of Physics, Nankai University, Tianjin 300071, PR China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Tian
authors.affiliation: Research Center of Basic Medical Sciences & Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin Medical University, Tianjin 300070, PR China.
authors.forename: Haifang
authors.initials: H
authors.lastname: Yin
authors.affiliation: Research Center of Basic Medical Sciences & Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin Medical University, Tianjin 300070, PR China; School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, Tianjin 300070, PR China. Electronic address: wangyinsong@tijmu.edu.cn.
authors.forename: Yinsong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Research Center of Basic Medical Sciences & Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin Medical University, Tianjin 300070, PR China. Electronic address: zhangning@tijmu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002144:Callithrix; D002470:Cell Survival; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006415:Hematoporphyrins / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D007770:L-Lactate Dehydrogenase / Q000097:blood; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D010778:Photochemotherapy / Q000379:methods; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D006415:Hematoporphyrins; D011092:Polyethylene Glycols; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase
keywords: Chemotherapy; Doxorubicin; Hematoporphyrin; Photodynamic therapy; Tumor targeting