Photodynamic therapy (PDT) has been showing great potential in cancer treatment. However, the efficacy of PDT is always limited by the intrinsic hypoxic tumor microenvironment (TME) and the low accumulation efficiency of photosensitizers in tumors. To address the issue, a multifunctional hollow multilayer nanoplatform (H‐MnO2@TPyP@Bro) comprising manganese dioxide, porphyrin (TPyP) and bromelain (Bro), is developed for enhanced photodynamic therapy. MnO2 catalyzes the intracellular hydrogen peroxide (H2O2) to produce oxygen (O2), reversing the hypoxic TME in vivo. The generated O2 is converted into singlet oxygen (1O2) by the TPyP shell under near‐infrared light, which can inhibit tumor proliferation. Meanwhile, the Bro can digest collagen in the extracellular matrix around the tumor, and can promote the accumulation of H‐MnO2@TPyP@Bro in the deeper tumor tissue, further improving the therapeutic effect of PDT. In addition, MnO2 can react with the overexpressed glutathione in TME to release Mn2+. Consequently, Mn2+ not only induces chemo‐dynamic therapy based on Fenton reaction by converting H2O2 into hydroxyl radicals, but also activates the Mn2+‐based magnetic resonance imaging. Therefore, the developed H‐MnO2@TPyP@Bro nanoplatform can effectively modulate the unfavorable TME and overcome the limitations of conventional PDT for cancer diagnostic and therapeutic.

Chemodynamic therapy (CDT) as a catalytic anticancer strategy utilizes transition metal ions to initiate the Fenton reaction to produce high levels of cytotoxic hydroxyl radicals(·OH) in situ. Nevertheless, current existing CDTs are normally restricted by the high levels of existing antioxidant molecules and/or enzymes, such as glutathione (GSH) and thioredoxin reductase (TrxR), in a tumor internal environment, which could suppress CDT via ·OH depletion. Herein, to enhance ·OH-induced cellular damage by CDT, a self-assembled copper-selenocysteine nanoparticles (Cu-SeC NPs) was fabricated through a one-pot process. In our design, once Cu-SeC NPs were endocytosed by tumor cells, Cu2+ was reduced to Cu+ by cellular GSH, promoting in situ Fenton-like reactions to trigger ·OH rapid production in cells as well as the depletion of GSH. Furthermore, the gradually released selenocysteine can inhibit TrxR activity to weaken the protection of antioxidant systems and provide a favorable microenvironment for CDT. As a result, both paths synergistically resulted in massive reactive oxygen species (ROS) accumulation and amplified oxidative stress in tumor sites for enhanced CDT. As a new intelligent anticancer nanoplatform, Cu-SeC NPs exhibit synergistic antitumor effects with negligible systemic toxicity. Thus, the proposed strategy provides a new avenue for further development of progressive therapeutic systems.

Long non-coding RNAs (lncRNAs) regulate neurological damage in cerebral ischemia-reperfusion injury (CIRI). This study aimed to investigate the biological roles of lncRNA CEBPA-AS1 in CIRI. Middle cerebral artery occlusion and ischemia-reperfusion injury (MCAO/IR) rat model and oxygen-glucose deprivation and reoxygenation (OGD/R) cell lines were generated; the expression of CEBPA-AS1 was evaluated by qRT-PCR. The effects of CEBPA-AS1 on cell apoptosis and nerve damage were examined. The downstream microRNA (miRNA) and mRNA of CEBPA-AS1 were predicted and verified. We found that overexpression of CEBPA-AS1 could attenuate MCAO/IR-induced nerve damage and neuronal apoptosis in the rat model. Knockdown of CEBPA-AS1 aggravated cell apoptosis and enhanced the production of LDH and MDA in the OGD/R cells.Upon examining the molecular mechanisms, we found that CEBPA-AS1 stimulated APPL1 expression by combining with miR-340-5p, thereby regulating the APPL1/LKB1/AMPK pathway. In the rescue experiments, CEBPA-AS1 overexpression was found to attenuate OGD/R-induced cell apoptosis and MCAO/IR induced nerve damage, while miR-340-5p reversed these effects of CEBPA-AS1. In conclusion, CEBPA-AS1 could decrease CIRI by sponging miR-340-5, regulating the APPL1/LKB1/AMPK pathway.