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Acid-responsive H₂-releasing Fe nanoparticles for safe and effective cancer therapy

Kou, Zhu, Zhao, Penghe, Wang, Zhihao, Jin, Zhaokui, Chen, Lihua, Su, Bao-Lian, He, Qianjun
Journal of materials chemistry B 2019 v.7 no.17 pp. 2759-2765
carboxymethylcellulose, energy metabolism, homeostasis, hydrogen, image analysis, intravenous injection, iron, nanomedicine, nanoparticles, neoplasms, solubility, therapeutics
Hydrogen therapy is an emerging and promising strategy for treatment of inflammation-related diseases owing to the excellent bio-safety of hydrogen molecules (H₂), but is facing a challenge that the H₂ concentration at the local disease site is hardly accumulated because of its high diffusibility and low solubility, limiting the efficacy of hydrogen therapy. Herein, we propose a nanomedicine strategy of imaging-guided tumour-targeted delivery and tumour microenvironment-triggered release of H₂ to address this issue, and develop a kind of biocompatible carboxymethyl cellulose (CMC)-coated/stabilized Fe (Fe@CMC) nanoparticle with photoacoustic imaging (PAI), tumour targeting and acid responsive hydrogen release properties for cancer therapy. The Fe@CMC nanoparticles have demonstrated high intratumoural accumulation capability, high acid responsiveness, excellent PAI performance, selective cancer-killing effect and high bio-safety in vitro and in vivo. Effective inhibition of tumour growth is achieved by intravenous injection of the Fe@CMC nanoparticles, and the selective anti-cancer mechanism of Fe@CMC is discovered to be originated from the energy metabolism homeostasis regulatory function of the released H₂. The proposed nanomedicine-mediated hydrogen therapy strategy will open a new window for precise, high-efficacy and safe cancer treatment.