The integration of reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) holds great promise for enhanced anticancer effects. Herein, we report biodegradable cancer cell membrane-coated mesoporous copper/manganese silicate nanospheres (mCMSNs) with homotypic targeting ability to the cancer cell lines and enhanced ROS generation through singlet oxygen ( 1 O 2 ) production and glutathione (GSH)-activated Fenton reaction, showing excellent CDT/PDT synergistic therapeutic effects. We demonstrate that mCMSNs are able to relieve the tumor hypoxia microenvironment by catalytic decomposition of endogenous H 2 O 2 to O 2 and further react with O 2 to produce toxic 1 O 2 with a 635 nm laser irradiation. GSH-triggered mCMSNs biodegradation can simultaneously generate Fenton-like Cu + and Mn 2+ ions and deplete GSH for efficient hydroxyl radical (•OH) production. The specific recognition and homotypic targeting ability to the cancer cells were also revealed. Notably, relieving hypoxia and GSH depletion disrupts the tumor microenvironment (TME) and cellular antioxidant defense system, achieving exceptional cancertargeting therapeutic effects in vitro and in vivo. The cancer cells growth was significantly inhibited. Moreover, the released Mn 2+ can also act as an advanced contrast agent for cancer magnetic resonance imaging (MRI). Thus, together with photosensitizers, Fenton agent provider and MRI contrast effects along with the modulating of the TME allow mCMSNs to realize MRI-monitored enhanced CDT/PDT synergistic therapy. It provides a paradigm to rationally design TMEresponsive and ROS-involved therapeutic strategies based on a single polymetallic silicate nanomaterial with enhanced anticancer effects.
The therapeutic effect of reactive oxygen species (ROS)-involved cancer therapies is significantly limited by shortage of oxy-substrates, such as hypoxia in photodynamic therapy (PDT) and insufficient hydrogen peroxide (H 2 O 2 ) in chemodynamic therapy (CDT). Here, we report a H 2 O 2 /O 2 self-supplying nanoagent, (MSNs@CaO 2 -ICG)@LA, which consists of manganese silicate (MSN)-supported calcium peroxide (CaO 2 ) and indocyanine green (ICG) with further surface modification of phase-change material lauric acid (LA). Under laser irradiation, ICG simultaneously generates singlet oxygen and emits heat to melt the LA. The exposed CaO 2 reacts with water to produce O 2 and H 2 O 2 for hypoxia-relieved ICG-mediated PDT and H 2 O 2 -supplying MSN-based CDT, acting as an open source strategy for ROS production. Additionally, the MSNs-induced glutathione depletion protects ROS from scavenging, termed reduce expenditure. This open source and reduce expenditure strategy is effective in inhibiting tumor growth both in vitro and in vivo, and significantly improves ROS generation efficiency from multi-level for ROS-involved cancer therapies.
BackgroundSub-therapeutic antibiotics are widely used as growth promoters in the poultry industry; however, the resulting antibiotic resistance threatens public health. A plant-derived growth promoter, Macleaya cordata extract (MCE), with effective ingredients of benzylisoquinoline alkaloids, is a potential alternative to antibiotic growth promoters. Altered intestinal microbiota play important roles in growth promotion, but the underlying mechanism remains unknown.ResultsWe generated 1.64 terabases of metagenomic data from 495 chicken intestinal digesta samples and constructed a comprehensive chicken gut microbial gene catalog (9.04 million genes), which is also the first gene catalog of an animal’s gut microbiome that covers all intestinal compartments. Then, we identified the distinctive characteristics and temporal changes in the foregut and hindgut microbiota. Next, we assessed the impact of MCE on chickens and gut microbiota. Chickens fed with MCE had improved growth performance, and major microbial changes were confined to the foregut, with the predominant role of Lactobacillus being enhanced, and the amino acids, vitamins, and secondary bile acids biosynthesis pathways being upregulated, but lacked the accumulation of antibiotic-resistance genes. In comparison, treatment with chlortetracycline similarly enriched some biosynthesis pathways of nutrients in the foregut microbiota, but elicited an increase in antibiotic-producing bacteria and antibiotic-resistance genes.ConclusionThe reference gene catalog of the chicken gut microbiome is an important supplement to animal gut metagenomes. Metagenomic analysis provides insights into the growth-promoting mechanism of MCE, and underscored the importance of utilizing safe and effective growth promoters.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0590-5) contains supplementary material, which is available to authorized users.
Wearable sweat sensors have spearheaded the thrust toward personalized health monitoring with continuous, real-time, and molecular-level insight in a noninvasive manner. However, effective sweat sampling still remains a huge challenge. Here, we introduce an intelligent Janus textile band that bridges the gap between self-pumping sweat collection, comfortable epidemic microclimate, and sensitive electrochemical biosensing via an integrated wearable platform. The dominant sweat sampling configuration is a textile with Janus wettability, which is fabricated by electrospinning a hydrophobic polyurethane (PU) nanofiber array onto superhydrophilic gauze. Based on a contact-pumping model, the Janus textile can unidirectionally and thoroughly transport sweat from skin (hydrophobic side) to embedded electrode surface (hydrophilic side) with epidemic comfort. On-body experimentation reveals that the sensitive detection of multiple biomarkers including glucose, lactate, K + , and Na + is achieved in the pumped sweat. Such smart Janus textile bands can effectively drain epidermal sweat to targeted assay sites via interface modifications, representing a reinforced and controlled biofluids analysis pathway with physiological comfort.
An efficient three-dimensional (3D) hybrid material of nitrogen-doped graphene sheets (N-RGO) supporting molybdenum disulfide (MoS2) nanoparticles with high-performance electrocatalytic activity for hydrogen evolution reaction (HER) is fabricated by using a facile hydrothermal route. Comprehensive microscopic and spectroscopic characterizations confirm the resulting hybrid material possesses a 3D crumpled few-layered graphene network structure decorated with MoS2 nanoparticles. Electrochemical characterization analysis reveals that the resulting hybrid material exhibits efficient electrocatalytic activity toward HER under acidic conditions with a low onset potential of 112 mV and a small Tafel slope of 44 mV per decade. The enhanced mechanism of electrocatalytic activity has been investigated in detail by controlling the elemental composition, electrical conductance and surface morphology of the 3D hybrid as well as Density Functional Theory (DFT) calculations. This demonstrates that the abundance of exposed active sulfur edge sites in the MoS2 and nitrogen active functional moieties in N-RGO are synergistically responsible for the catalytic activity, whilst the distinguished and coherent interface in MoS2/N-RGO facilitates the electron transfer during electrocatalysis. Our study gives insights into the physical/chemical mechanism of enhanced HER performance in MoS2/N-RGO hybrids and illustrates how to design and construct a 3D hybrid to maximize the catalytic efficiency.
Cell membrane camouflaged nanoparticles (NPs) have been increasingly explored to leverage natural cellular functions and adapt to various biomedical applications. Herein, we report an OMV-CC hybrid membrane, which consists of a bacterial outer membrane vesicle (OMV) and B16-F10 cancer cell (CC) membrane, and successfully coat it onto hollow polydopamine (HPDA) NPs. We harness the advantage of OMV immunotherapy together with HPDA-mediated photothermal therapy (PTT) to improve the antitumor efficacy toward melanoma. When injected intravenously via the tail vein, HPDA@[OMV-CC] NPs homogeneously target melanoma and activate the immune response by rapidly stimulating dendritic cell (DC) maturation in lymph nodes in the vaccinated mice. Our results show that the antitumor immune response and PTT reciprocally potentiate the therapeutic ability and fully eradicate melanoma without notable adverse effects. The homogeneous-target and immune activation hybrid biomimetic membrane provides the adaptability to various synergistic therapeutic and imaging applications by incorporating payload with application-specific functions.
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