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Nanoscale covalent organic polymers as a biodegradable nanomedicine for chemotherapy-enhanced photodynamic therapy of cancer

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Abstract

Recently, covalent-organic polymers (COPs), which covalently cross-link different types of organic molecules to form organic network structures, have received significant attention in various fields. However, the design of COPs that allows them to act as therapeutic agents remains to be explored. In the present study, a new class of COPs was fabricated by cross-linking the photosensitizer meso-tetra(p-hydroxyphenyl) porphine (THPP) to a chemotherapeutic pro-drug, cis-platinum (IV); the latter also acts as a reduction-responsive linker. After further conjugation with polyethylene glycol (PEG) in this one-pot reaction, we obtained THPP-Pt-PEG COPs, which can be stored in a lyophilized form and occur as stable nanoparticles in aqueous solution. The THPP-Pt-PEG COPs are effective in killing cancer cells through photodynamic treatment, and exhibited reduction-responsive degradation/drug release behaviors. Upon intravenous injection, the COPs, with a long blood circulation time, showed efficient tumor accumulation. Interestingly, we revealed that after injection of THPP-Pt-PEG COPs, tumors on mice exhibited greatly improved vascular perfusion and largely relieved tumor hypoxia, which favored subsequent photodynamic treatment. Hence, the combined chemo-photodynamic therapy of the COPs offers a remarkably improved therapeutic outcome compared to that with mono-therapies. This work presents a COP-based nanomedicine with high drug loading, lyophilizable formulation, prolonged blood half-life, efficient tumor passive homing, inherent biodegradability, and multiple therapeutic functions to achieve enhanced cancer combination therapy, with promise for clinical translation.

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Acknowledgements

This article was partially supported by the National Basic Research Programs of China (No. 2016YFA0201200), the National Natural Science Foundation of China (No. 51525203), Collaborative Innovation Center of Suzhou Nano Science and Technology, and a Project Funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.

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  1. Hairong Wang and Wenwen Zhu contributed equally to this work.

Authors and Affiliations

  1. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon Based Functional Materials and Devices, Soochow University, Suzhou, 215123, China

    Hairong Wang, Wenwen Zhu, Liangzhu Feng, Qian Chen, Yu Chao, Ziliang Dong & Zhuang Liu

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  1. Hairong Wang
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  2. Wenwen Zhu
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  3. Liangzhu Feng
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  4. Qian Chen
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  7. Zhuang Liu
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Correspondence to Zhuang Liu.

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Nanoscale covalent organic polymers as a biodegradable nanomedicine for chemotherapy-enhanced photodynamic therapy of cancer

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Wang, H., Zhu, W., Feng, L. et al. Nanoscale covalent organic polymers as a biodegradable nanomedicine for chemotherapy-enhanced photodynamic therapy of cancer. Nano Res. 11, 3244–3257 (2018). https://doi.org/10.1007/s12274-017-1858-y

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