Oxygen-producing proenzyme hydrogels for photodynamic-mediated metastasis-inhibiting combinational therapy. Issue 26 (17th June 2021)

• Record Type: Journal Article
• Authors: Liu, Jiansheng; Qing, Xueqin; Zhang, Qin; Yu, Ningyue; Ding, Mengbin; Li, Zhaohui; Zhao, Zhen; Zhou, Zhiling; Li, Jingchao
• Is Part Of: Journal of materials chemistry. Volume 9:Issue 26(2021)
• Page Start: 5255
• Page End: 5263
• Publication Date: 2021-06-17
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/d1tb01009c
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : An oxygen-producing proenzyme hydrogel with near-infrared photoactivatable enzymatic activity was developed for photodynamic therapy enabled metastasis-inhibiting combinational therapy of breast cancer. Abstract : Photodynamic therapy (PDT) has provided a promising approach for the treatment of solid tumors, while the therapeutic efficacy is often limited due to the hypoxic tumor microenvironment, resulting in tumor metastasis. Herein, we report an oxygen-producing proenzyme hydrogel (OPeH) with photoactivatable enzymatic activity for PDT enabled metastasis-inhibiting combinational therapy of breast cancer. This OPeH based on alginate is composed of protoporphyrin IX (PpIX) conjugated manganese oxide (MnO2 ) nanoparticles, which act as both the photosensitizer and oxygen-producing agent, and singlet oxygen ( 1 O2 )-responsive proenzyme nanoparticles. In the hypoxic and acidic tumor microenvironment, MnO2 can generate 1 O2 to promote PpIX-mediated PDT with an amplified 1 O2 generation efficiency, which also triggers the cleavage of 1 O2 -responsive linkers and cascade activation of proenzymes for cancer cell death. This combinational therapy upon photoactivation not only greatly inhibited the tumor growth, but also suppressed lung metastasis in a mouse xenograft breast tumor model, which is impossible in the case of PDT alone. This study thus provides a proenzyme hydrogel platform with photoactivatable activity for metastasis-inhibiting cancer therapy with high efficacy and safety.