Theranostics 2019; 9(23):6867-6884. doi:10.7150/thno.37586 This issue Cite

Research Paper

A tumor microenvironment responsive biodegradable CaCO3/MnO2- based nanoplatform for the enhanced photodynamic therapy and improved PD-L1 immunotherapy

Yanlei Liu1,2, Yunxiang Pan1, Wen Cao1, Fangfang Xia1, Bin Liu1, Jiaqi Niu1, Gabriel Alfranca1, Xiyang Sun3, Lijun Ma3, Jesus Martinez de la Fuente1, Jie Song1, Jian Ni1, Daxiang Cui1,2✉

1. Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Centre for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P.R. China
2. National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, Shanghai 200240, P. R. China
3. Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai, 200336, China.

Citation:
Liu Y, Pan Y, Cao W, Xia F, Liu B, Niu J, Alfranca G, Sun X, Ma L, Fuente JMdl, Song J, Ni J, Cui D. A tumor microenvironment responsive biodegradable CaCO3/MnO2- based nanoplatform for the enhanced photodynamic therapy and improved PD-L1 immunotherapy. Theranostics 2019; 9(23):6867-6884. doi:10.7150/thno.37586. https://www.thno.org/v09p6867.htm
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Abstract

Graphic abstract

The low efficiency of photodynamic therapy (PDT) is caused by tumor hypoxia and the adaptive immune resistance/evasion of tumor cells, while the currently emerging immune checkpoint therapy restores the intrinsic immune capacities but can't directly attack the tumor cells.

Methods: Herein we report an integrated nanoplatform that combines PDT with immunotherapy to enhance photodynamic therapeutic effects and simultaneously inhibit tumor cells resistance/evasion. To achieve this, we fabricated Mn@CaCO3/ICG nanoparticles and loaded them with PD-L1-targeting siRNA.

Results: Thanks to the protection of CaCO3 on the loaded ICG and the oxygen produced by MnO2, an enhanced photodynamic therapeutic effect in vitro was observed. In vivo experiments demonstrated that the nanoplatform could efficiently deliver the loaded drug to the tumor tissues and significantly improve tumor hypoxia, which further contributes to the therapeutic effect of PDT in vivo. Moreover, the synergistic benefits derived from the siRNA, which silenced the checkpoint gene PD-L1 that mediates the immune resistance/evasion, resulted in a surprising therapeutic effect to rouse the immune system.

Conclusions: The combination treatment strategy has great potential to be developed as a new and robust method for enhanced PDT therapy with high efficiency and a powerful antitumor immune response based on PD-L1 blockade.

Keywords: MnO2, Photodynamic therapy, PD-L1, Tumor immunotherapy


Citation styles

APA
Liu, Y., Pan, Y., Cao, W., Xia, F., Liu, B., Niu, J., Alfranca, G., Sun, X., Ma, L., Fuente, J.M.d.l., Song, J., Ni, J., Cui, D. (2019). A tumor microenvironment responsive biodegradable CaCO3/MnO2- based nanoplatform for the enhanced photodynamic therapy and improved PD-L1 immunotherapy. Theranostics, 9(23), 6867-6884. https://doi.org/10.7150/thno.37586.

ACS
Liu, Y.; Pan, Y.; Cao, W.; Xia, F.; Liu, B.; Niu, J.; Alfranca, G.; Sun, X.; Ma, L.; Fuente, J.M.d.l.; Song, J.; Ni, J.; Cui, D. A tumor microenvironment responsive biodegradable CaCO3/MnO2- based nanoplatform for the enhanced photodynamic therapy and improved PD-L1 immunotherapy. Theranostics 2019, 9 (23), 6867-6884. DOI: 10.7150/thno.37586.

NLM
Liu Y, Pan Y, Cao W, Xia F, Liu B, Niu J, Alfranca G, Sun X, Ma L, Fuente JMdl, Song J, Ni J, Cui D. A tumor microenvironment responsive biodegradable CaCO3/MnO2- based nanoplatform for the enhanced photodynamic therapy and improved PD-L1 immunotherapy. Theranostics 2019; 9(23):6867-6884. doi:10.7150/thno.37586. https://www.thno.org/v09p6867.htm

CSE
Liu Y, Pan Y, Cao W, Xia F, Liu B, Niu J, Alfranca G, Sun X, Ma L, Fuente JMdl, Song J, Ni J, Cui D. 2019. A tumor microenvironment responsive biodegradable CaCO3/MnO2- based nanoplatform for the enhanced photodynamic therapy and improved PD-L1 immunotherapy. Theranostics. 9(23):6867-6884.

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