Theranostics 2018; 8(6):1558-1574. doi:10.7150/thno.22989

Research Paper

Oxygen-generating Hybrid Polymeric Nanoparticles with Encapsulated Doxorubicin and Chlorin e6 for Trimodal Imaging-Guided Combined Chemo-Photodynamic Therapy

DanRong Hu, LiJuan Chen, Ying Qu, JinRong Peng, BingYang Chu, Kun Shi, Ying Hao, Lin Zhong, MengYao Wang, ZhiYong Qian

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center. Chengdu 610041, PR China

Abstract

The combination of chemotherapy with photodynamic therapy (PDT) has attracted broad attention as it can overcome limitations of conventional chemo-treatment by using different modes of action. However, the efficacy of PDT to treat solid tumors is severely affected by hypoxia in tumors.

Methods: In this study, we developed oxygen-generating theranostic nanoparticles (CDM NPs) by hierarchically assembling doxorubicin (DOX), chlorin e6 (Ce6) and colloidal manganese dioxide (MnO2) with poly (ε-caprolactone-co-lactide)-b-poly (ethylene glycol)-b-poly (ε-caprolactone-co-lactide) for treating breast cancer. The in vitro and in vivo antitumor efficacy and imaging performance were investigated.

Results: The theranostic nanoparticles showed high stability and biocompatibility both in vitro and in vivo. MnO2 within the nanoparticles could trigger decomposition of excessive endogenous H2O2 in the tumor microenvironment to generate oxygen in-situ to relieve tumor hypoxia. With enhanced oxygen generation, the PDT effect was significantly improved under laser-irradiation. More importantly, this effect together with that of DOX was able to dramatically promote the combined chemotherapy-PDT efficacy of CDM NPs in an MCF-7 tumor-bearing mouse model. Furthermore, the real-time tumor accumulation of the nanocomposites could be monitored by fluorescence imaging, photoacoustic (PA) imaging and magnetic resonance imaging (MRI).

Conclusion: The designed CDM NPs are expected to provide an alternative way of improving antitumor efficacy by combined chemo-PDT further enhanced by oxygen generation, and would have broad applications in cancer theranostics.

Keywords: Multifunctional nanoparticles, manganese dioxide nanoparticles, hypoxia relieve, oxygen generation, combination therapy, theranostics

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How to cite this article:
Hu D, Chen L, Qu Y, Peng J, Chu B, Shi K, Hao Y, Zhong L, Wang M, Qian Z. Oxygen-generating Hybrid Polymeric Nanoparticles with Encapsulated Doxorubicin and Chlorin e6 for Trimodal Imaging-Guided Combined Chemo-Photodynamic Therapy. Theranostics 2018; 8(6):1558-1574. doi:10.7150/thno.22989. Available from http://www.thno.org/v08p1558.htm