Theranostics 2018; 8(11):2939-2953. doi:10.7150/thno.24015

Research Paper

Cascade-amplifying synergistic effects of chemo-photodynamic therapy using ROS-responsive polymeric nanocarriers

Chun-Yang Sun1*, Ziyang Cao2*, Xue-Jun Zhang3, Rong Sun4, Chun-Shui Yu1✉, Xianzhu Yang2✉

1. Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
2. Institutes for Life Sciences, School of Medicine and National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, Guandong 510006, P. R. China
3. School of Medical Imaging, Tianjin Medical University, Tianjin 300203, P.R. China
4. School of Biological and Chemical Engineering, Zhejiang University of Science & Technology, Hangzhou, Zhejiang 310023, P. R. China
*These authors contributed equally.

Abstract

The simple integration of chemotherapeutic drugs and photosensitizers (PSs) into the same nanocarriers only achieves a combination of chemo-photodynamic therapy but may not confer synergistic effects. The boosted intracellular release of chemotherapeutic drugs during the photodynamic therapy (PDT) process is necessary to achieve a cascade of amplified synergistic therapeutic effects of chemo-photodynamic therapy.

Methods: In this study, we explored an innovative hyperbranched polyphosphate (RHPPE) containing a singlet oxygen (SO)-labile crosslinker to boost drug release during the PDT process. The photosensitizer chlorin e6 (Ce6) and doxorubicin (DOX) were simultaneously loaded into RHPPE nanoparticles (denoted as SOHNPCe6/DOX). The therapeutic efficacy of SOHNPCe6/DOX against drug-resistant cancer was evaluated in vitro and in vivo.

Results: Under 660-nm light irradiation, SOHNPCe6/DOX can produce SO, which not only induces PDT against cancer but also cleaves the thioketal linkers to destroy the nanoparticles. Subsequently, boosted DOX release can be achieved, activating a chemotherapy cascade to synergistically destroy the remaining tumor cells after the initial round of PDT. Furthermore, SOHNPCe6/DOX also efficiently detected the tumor area by photoacoustic/magnetic resonance bimodal imaging. Under the guidance of bimodal imaging, the laser beam was precisely focused on the tumor areas, and subsequently, SOHNPCe6/DOX realized a cascade of amplified synergistic chemo-photodynamic therapeutic effects. High antitumor efficacy was achieved even in a drug-resistant tumor model.

Conclusion: The designed SOHNPCe6/DOX with great biocompatibility is promising for use as a co-delivery carrier for combined chemo-photodynamic therapy, providing an alternative avenue to achieve a cascade of amplified synergistic effects of chemo-photodynamic therapy for cancer treatment.

Keywords: ROS responsive, chemo-photodynamic therapy, on-demand drug release, drug-resistant cancer, synergistic therapy

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How to cite this article:
Sun CY, Cao Z, Zhang XJ, Sun R, Yu CS, Yang X. Cascade-amplifying synergistic effects of chemo-photodynamic therapy using ROS-responsive polymeric nanocarriers. Theranostics 2018; 8(11):2939-2953. doi:10.7150/thno.24015. Available from http://www.thno.org/v08p2939.htm