Biomimetic Nanobomb for Synergistic Therapy with Inhibition of Cancer Stem Cells.

Cancer stem cells (CSCs), a type of cell with self-renewal, unlimited proliferation, and insensitivity to common physical and chemical factors, are the key to cancer metastasis, recurrence, and chemo-resistance. Available CSCs inhibition strategies are mainly based on small molecule drugs, yet are limited by their off-target toxicity. The link between CSCs and non-CSCs interconversion is difficult to sever. In this work, a nanotherapeutic strategy based on MnOx -loaded polydopamine (MnOx /PDA) nanobombs with chemodynamic, photodynamic, photothermal and biodegradation properties to inhibit CSCs and non-CSCs concurrently is reported. The MnOx /PDA nanobombs can directly disrupt the microenvironment and tumorigenic capacity of CSCs by generating hyperthermia, oxidative stress and alleviating hypoxia. The markers of CSCs are subsequently downregulated, leading to the clearance of CSCs. Meanwhile, the synergistic therapy mediated by MnOx /PDA nanobombs can directly ablate the bulk tumor cells, thus cutting off the supply of CSCs transformation. For tumor targeting, MnOx /PDA is coated with macrophage membrane. The final tumor inhibition rate of the synergistic therapy is 70.8% in colorectal cancer (CRC) model. Taken together, the present work may open up the exploration of nanomaterial-based synergistic therapy for the simultaneous elimination of therapeutically resistant CSCs and non-CSCs.

An Integrating Platform of Ratiometric Fluorescent Adsorbent for Unconventional Real-Time Removing and Monitoring of Copper Ions.

Nondegradable heavy metals have caused great dangers to the environment and human health. Combining stimuli-responsive materials with conventional MOF-based adsorbents has been considered an effective method to generate intelligent adsorbents for superior control over the adsorption process. Herein, a smart MOF-based ratiometric fluorescent adsorbent was designed to accurately monitor the progression of the removal of copper ions with dual-emitting fluorescence signal. Unlike the traditional difunctional materials, this delicately designed platform overcomes the huge energy gap to achieve two functions simultaneously. This unconventional platform provides a reliable fluorescent response toward Cu2+ during the removing process, changing linearly related to the degree of the adsorption process, which holds extreme promise in effectively monitoring the adsorption process. The underlying relationship of the adsorption and fluorescence response process toward copper was investigated by density functional theory (DFT) calculations. In particular, because of the favorable ion binding affinity of ZIF-8 and self-calibrating effect of RhB, the as-prepared smart adsorbent demonstrates a superior adsorption performance of 608 mg g-1, broad response range (0.05-200 ppm, 2.07 × 10-7to 8.29 × 10-4 M), ultrahigh sensitivity (0.04 ppm, 1.91 × 10-7 M) toward Cu2+ and strong anti-interference ability. This smart adsorbent opens an intelligent pathway to promote substantial advancements in the fields of environmental monitoring and industrial waste management.

Dietary flavonoids fisetin and myricetin: dual inhibitors of Plasmodium falciparum falcipain-2 and plasmepsin II.

Malaria is one of the most devastating infectious diseases in the developing world. Until now, only one candidate malaria vaccine RTS,S/AS01 has shown modest protection in phase 3 trial in African infants. Hence the treatment of malaria still depends on the current chemotherapeutic drugs. Considering the resistance of malaria parasites to almost all used antimalarial drugs, aiming at multi-targets rather than a single target will be a more promising strategy. Previous studies have shown that myricetin and fisetin exhibited in vitro antimalarial activity against Plasmodium falciparum, but very little research focused on the molecular mechanism for their parasiticidal activity. The cysteine protease falcipain-2 and aspartic protease plasmepsin II have long been considered as important antimalarial drug targets, especially combined inhibition of these two proteases. In this study, we determined that myricetin and fisetin are dual inhibitors of falcipain-2 and plasmepsin II, which might account for their antimalarial properties. Overall, the dual inhibition of falcipain-2 and plasmepsin II by myricetin and fisetin has shed light on a possible mechanism for their antimalarial activity and provided a rationale for further development as antimalarial drugs.