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PCN-Fe(III)-PTX nanoparticles for MRI guided high efficiency chemo-photodynamic therapy in pancreatic cancer through alleviating tumor hypoxia

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Abstract

As nanomedicine-based clinical strategies have continued to develop, the possibility of combining chemotherapy and singlet oxygen-dependent photodynamic therapy (PDT) to treat pancreatic cancer (PaC) has emerged as a viable therapeutic modality. The efficacy of such an approach, however, is likely to be constrained by the mechanisms of drug release and tumor oxygen levels. In the present study, we developed an Fe(III)-complexed porous coordination network (PCN) which we then used to encapsulate PTX (PCN-Fe(III)-PTX) nanoparticles (NPs) in order to treat PaC via a combination of chemotherapy and PDT. The resultant NPs were able to release drug in response to both laser irradiation and pH changes to promote drug accumulation within tumors. Furthermore, through a Fe(III)-based Fenton-like reaction these NPs were able to convert H2O2 in the tumor site to O2, thereby regulating local hypoxic conditions and enhancing the efficacy of PDT approaches. Also these NPs were suitable for use as a T1-MRI weighted contrast agent, making them viable for monitoring therapeutic efficacy upon treatment. Our results in both cell line and animal models of PaC suggest that these NPs represent an ideal agent for mediating effective MRI-guided chemotherapy-PDT, giving them great promise for the clinical treatment of PaC.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81527803, 81420108018, U1432114, 81550110258, 8161101589, 81650410654 and 31971292), National Key R&D Program of China (Nos. 2018YFC0115900 and 2018YFC0910601), Key Breakthrough Program of Chinese Academy of Sciences (No. KGZD-EW-T06), Zhejiang Science and Technology Project (No. 2019C03077), the Hundred Talents Program of Chinese Academy of Sciences (No. 2010-735), Youth Natural Science Fund Project of Zhejiang Province (No. LQ19H180004), Natural Science Fund Project of Ningbo City (No. 2018A610380), and Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province (No. 2019E10020). We acknowledge Ruifen Zou for help in animal experiments, and Ting Xue for help of Material characterization.

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  1. Tao Zhang, Zhenqi Jiang, and Libin Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Ultrasound, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, China

    Tao Zhang & Pintong Huang

  2. Cixi Institute of Biomedical Engineering, CAS Key Laboratory of Magnetic Materials and Devices, & Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, China

    Zhenqi Jiang, Chunshu Pan, Shan Sun, Chuang Liu, Zihou Li, Wenzhi Ren & Aiguo Wu

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    Zhenqi Jiang

  4. Department of Ultrasound, Ningbo First Hospital, Ningbo, 315010, China

    Libin Chen

  5. Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, 315016, China

    Wenzhi Ren

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  1. Tao Zhang
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Correspondence to Wenzhi Ren, Aiguo Wu or Pintong Huang.

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PCN-Fe(III)-PTX nanoparticles for MRI guided high efficiency chemo-photodynamic therapy in pancreatic cancer through alleviating tumor hypoxia

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Zhang, T., Jiang, Z., Chen, L. et al. PCN-Fe(III)-PTX nanoparticles for MRI guided high efficiency chemo-photodynamic therapy in pancreatic cancer through alleviating tumor hypoxia. Nano Res. 13, 273–281 (2020). https://doi.org/10.1007/s12274-019-2610-6

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