title: Targeted Chemo-Photodynamic Combination Platform Based on the DOX Prodrug Nanoparticles for Enhanced Cancer Therapy.
abstract: Chemo-photodynamic combination therapy has been received widespread attention in cancer treatment due to its excellent characteristics, such as reducing the adverse side effects of chemo-drugs and improving the therapeutic effects for various cancers. In this study, RGD and DOX was conjugated to PEG by thiol-ene addition and Schiff's base reaction, respectively, to prepare the targeted and pH-sensitive antitumor prodrug nanoparticles (RGD-PEG-DOX NPs, RGD-NPs). Subsequently, the photosensitizer chlorin e6 (Ce6) was encapsulated into RGD-NPs, thus obtaining a simple and efficient chemo-photodynamic combination platform (RGD-PEG-DOX/Ce6 NPs, RGD-NPs/Ce6). This nanoparticle possessed high drug loading property of both the chemo-drug and photosensitizer and could simultaneously release them under the mild acidic microenvironment of cancer cells, which was expected to realize the synchronization therapy of chemotherapy and photodynamic therapy (PDT). Compared with free DOX and Ce6, RGD-NPs/Ce6 could significantly improve the cellular uptake capacities of DOX and Ce6, resulting in the increased contents of ROS in cancer cells and effective cytotoxicity for tumor cells (MDA-MB-231 cells and MCF-7 cells) upon a laser radiation. The in vivo experiment showed that RGD-NPs/Ce6 displayed superior tumor targeting, accumulation, and retention ability than the other groups (free DOX, free Ce6 and NPs/Ce6), and thus significantly enhancing the antitumor effect in vivo with a laser radiation. In addition, the cardiotoxicity induced by DOX was thoroughly wiped out after being loaded and delivered by the nanoparticles according to the pathological analysis. Therefore, the targeted chemo-photodynamic combination therapeutic platform may be a promising candidate for enhanced cancer therapy.
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin 300192, P.R. China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin 300192, P.R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Huang
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin 300192, P.R. China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Ren
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin 300192, P.R. China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin 300192, P.R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University , Stanford, California 94305, United States.
authors.forename: Zhen
authors.identifier: http://orcid.org/0000-0001-8177-9463
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin 300192, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Chu
authors.affiliation: Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College , Tianjin 300192, P.R. China.
authors.forename: Jinjian
authors.identifier: http://orcid.org/0000-0001-5176-7613
authors.initials: J
authors.lastname: Liu
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D053758:Nanoparticles; D009369:Neoplasms; D010778:Photochemotherapy; D017319:Photosensitizing Agents; D011355:Prodrugs
chemical_list: D017319:Photosensitizing Agents; D011355:Prodrugs
keywords: DOX prodrug nanoparticles; cancer targeting; chemo-photodynamic combination therapy; codelivery; pH-responsive