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Light-activatable dual prodrug polymer nanoparticle for precise synergistic chemotherapy guided by drug-mediated computed tomography imaging.

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机构： [a]State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China [b]School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, PR China [c]Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, PR China [d]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China [e]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, PR China

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The synergistic efficacy and clinical application of light-responsive polymeric co-delivery systems are severely restricted by uncontrollable/imprecise drug loading, release, and adverse effects caused by the introduction of additional light-responsive molecules or contrast agents when diagnostic imaging is applied to guide therapy. Here, we report the design of a light-activatable dual prodrug polymer nanoparticle (DPP NP) for precise synergistic chemotherapy guided by drug-mediated computed tomography (DMCT) imaging without the introduction of any additional diagnostic imaging agent. DPP NP enables visible light-triggered prodrug polymer backbone cleavage and bioactive Pt(II) release in cancer cell/tumor site; the light-cleaved polymer fragments are further hydrolyzed to produce demethyl cantharidin (DMC). Notably, the drug loading ratio of Pt(IV) and DMC in DPP NP was fixed at an optimal value to achieve maximum synergistic cancer cell killing, which was kept even after cellular uptake, thereby resulting in enhanced synergistic antitumor efficacy both in vitro and in vivo. Because of the high content of the heavy metal Pt in the polymer chain, the spatial/temporal dynamic biodistribution as well as metabolism of DPP NP in vivo can be monitored by Pt DMCT imaging to guide the light irradiation parameters for optimized light-activatable synergistic chemotherapy. Guided by Pt DMCT imaging, DPP NP was able to achieve an improved light-activatable antitumor efficacy, with 75% tumors fully cured and low toxicity. The light-activatable DDP NP system exhibits tremendous potential as precise theranostic nanomedicine. STATEMENT OF SIGNIFICANCE: The synergistic efficacy and clinical application of light-responsive polymeric co-delivery systems are severely restricted by uncontrollable/imprecise drug loading, delivery, and release, as well as adverse effects caused by the introduction of additional light-responsive molecules or contrast agents when diagnostic imaging is applied to guide therapy. Herein, we report the design of a light-activatable dual prodrug polymer nanoparticle (DPP NP) for precise synergistic chemotherapy guided by drug-mediated computed tomography imaging without the introduction of any additional diagnostic imaging agents. Notably, the drug loading ratio of Pt(II) and DMC in DPP NP was fixed at an optimal value to achieve maximum synergistic cancer cell killing, which was kept even after cellular uptake, thereby resulting in enhanced synergistic antitumor efficacy both in vitro and in vivo. The light-activatable DDP NP system exhibits tremendous potential as precise theranostic nanomedicine. Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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出版当年[2018]版：

大类 | 1 区

工程技术

小类 | 1 区工程：生物医学 1 区材料科学：生物材料

最新[2025]版：

大类 | 1 区

医学

小类 | 1 区工程：生物医学 1 区材料科学：生物材料

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出版当年[2017]版：

Q1 MATERIALS SCIENCE, BIOMATERIALS Q1 ENGINEERING, BIOMEDICAL

最新[2023]版：

Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS

影响因子： 9.4 最新[2023版] 9.9 最新五年平均 6.383 出版当年[2017版] 7.16 出版当年五年平均 6.319 出版前一年[2016版] 6.638 出版后一年[2018版]

第一作者：

第一作者机构： [a]State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China [b]School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, PR China

通讯作者：

通讯机构： [a]State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China [b]School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, PR China [*1]State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China

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