Functionalized ZnMnFe2O4-PEG-FA nanoenzymes integrating diagnosis and therapy for targeting hepatic carcinoma guided by multi-modality imaging.

With its insidious onset and atypical early symptoms, hepatic carcinoma is one of the most common and malignant tumors in the world. Therefore, it is necessary to actively pursue efficient diagnostic and treatment modalities for this malignancy. Photothermal therapy (PTT) is a non-invasive treatment technique that can generate high temperatures locally to induce tumor cell death, but its effectiveness is limited by the tissue-penetration depth of infrared light. Enzyme-catalyzed therapy promotes the production of toxic hydroxyl groups (˙OH) from hydrogen peroxide in tumor cells in situ, but its efficacy is also affected by the catalytic efficiency of ˙OH. Thus, given the complexity of tumors, multimodal therapy is critical for cancer treatment. Herein, we report a novel biomimetic nanoparticle (NP) platform (ZnMnFe2O4-PEG-FA) that enables combined PTT and nanozyme-catalyzed therapy. Due to the excellent photothermal effect of ZnMnFe2O4-PEG-FA, these NPs can reach an ideal temperature and damage tumor cells under lower near-infrared laser power irradiation, while exhibiting enhanced catalytic ability, largely alleviating the limitations of conventional PTT and catalytic therapy. Hence, the combination of these two treatments can provide significantly greater cytotoxicity. Additionally, ZnMnFe2O4-PEG-FA NPs have excellent photoacoustic imaging and magnetic resonance imaging capabilities, which enable monitoring and can guide cancer treatment. Therefore, ZnMnFe2O4-PEG-FA NPs integrate the diagnosis and treatment of tumors. Hence, this study provides a potential model of combined cancer diagnosis and treatment, which could be applied as a multimodal antitumor strategy in clinical settings in the future.

CPF impedes cell cycle re-entry of quiescent lung cancer cells through transcriptional suppression of FACT and c-MYC.

Blockade of cell cycle re-entry in quiescent cancer cells is a strategy to prevent cancer progression and recurrence. We investigated the action and mode of action of CPF mixture (Coptis chinensis, Pinellia ternata and Fructus trichosanthis) in impeding a proliferative switch in quiescent lung cancer cells. The results indicated that CPF impeded cell cycle re-entry in quiescent lung cancer cells by reduction of FACT and c-MYC mRNA and protein levels, with concomitant decrease in H3K4 tri-methylation and RNA polymerase II occupancy at FACT and c-MYC promoter regions. Animals implanted with quiescent cancer cells that had been exposed to CPF had reduced tumour volume/weight. Thus, CPF suppresses proliferative switching through transcriptional suppression of FACT and the c-MYC, providing a new insight into therapeutic target and intervention method in impeding cancer recurrence.