Heme Oxygenase-1 Is Involved in the Repair of Oxidative Damage Induced by Oxidized Fish Oil in Litopenaeus vannamei by Sulforaphane.

Heme oxygenase-1 (HO-1), which could be highly induced under the stimulation of oxidative stress, functions in reducing the damage caused by oxidative stress, and sulforaphane (SFN) is an antioxidant. This study aims to investigate whether HO-1 is involved in the repair of oxidative damage induced by oxidized fish oil (OFO) in Litopenaeus vannamei by sulforaphane (SFN). The oxidative stress model of L. vannamei was established by feeding OFO feed (OFO accounts for 6%), and they were divided into the following four groups: control group (injected with dsRNA-EGFP and fed with common feed), dsRNA-HO-1 group (dsRNA-HO-1, common feed), dsRNA-HO-1 + SFN group (dsRNA-HO-1, supplement 50 mg kg-1 SFN feed), and SFN group (dsRNA-EGFP, supplement 50 mg kg-1 SFN feed). The results showed that the expression level of HO-1 in the dsRNA-HO-1 + SFN group was significantly increased compared with the dsRNA-HO-1 group (p < 0.05). The activities of SOD in muscle and GPX in hepatopancreas and serum of the dsRNA-HO-1 group were significantly lower than those of the control group, and MDA content in the dsRNA-HO-1 group was the highest among the four groups. However, SFN treatment increased the activities of GPX and SOD in hepatopancreas, muscle, and serum and significantly reduced the content of MDA (p < 0.05). SFN activated HO-1, upregulated the expression of antioxidant-related genes (CAT, SOD, GST, GPX, Trx, HIF-1α, Nrf2, prx 2, Hsp 70), and autophagy genes (ATG 3, ATG 5), and stabilized the expression of apoptosis genes (caspase 2, caspase 3) in the hepatopancreas (p < 0.05). In addition, knocking down HO-1 aggravated the vacuolation of hepatopancreas and increased the apoptosis of hepatopancreas, while the supplement of SFN could repair the vacuolation of hepatopancreas and reduce the apoptosis signal. In summary, HO-1 is involved in the repair of the oxidative damage induced by OFO in L. vannamei by SFN.

Engineering of an endogenous hydrogen sulfide responsive smart agent for photoacoustic imaging-guided combination of photothermal therapy and chemotherapy for colon cancer.

INTRODUCTION: Photothermal therapy can be synergistically combined with chemotherapy to improve the therapeutic effect for colon cancer. However, conventional therapeutic agents have side effects in normal tissues, limiting their application. OBJECTIVES: To reduce these side effects, a smart agent (Cur@HKUST-1@PVP) whose functionality is triggered by the high content of endogenous hydrogen sulfide in colon tumors was engineered for photoacoustic imaging-guided combination of photothermal therapy and chemotherapy for colon tumors. METHODS: After reacting with hydrogen sulfide, Cur@HKUST-1@PVP simultaneously generates CuS and releases curcumin. The generated CuS serves as an imaging agent for both photothermal therapy and photoacoustic imaging, while the released curcumin is used for chemotherapy. RESULTS: In vivo photoacoustic imaging experiments demonstrated that Cur@HKUST-1@PVP can be used for selectively imaging colon cancer tumors. In vivo experiments in mice for treatment suggested that the endogenous hydrogen sulfide-activated combination of photothermal therapy and chemotherapy has a better treatment effect that photothermal therapy or chemotherapy treatment alone. CONCLUSION: The endogenous hydrogen sulfide-activated Cur@HKUST-1@PVP agent developed herein shows great potential for the accurate diagnosis and effective treatment of colon cancer.

NIR light-controlled mitochondria-targeted delivery of carbon monoxide combined with histone deacetylase inhibition for synergistic anticancer therapy.

A multifunctional nanoplatform APIPB-MnCO@TPP@N,P-GQDs (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl) benzamide, TPP = triphenylphosphine, Mn = manganese, CO = carbon monoxide, and GQDs = graphene quantum dots), nanoplatform (1), was synthesized, which consists of a fluorescent N, P-doped GQDs carrier with its surface covalently functionalized by an CO donor APIPB-MnCO with histone deacetylases (HDAC) inhibitory property and a TPP derivative directing group. Nanoplatform (1) selectively localized in the mitochondria of HeLa cells to inhibit HDAC activity, and released CO upon 808 nm near-infrared light irradiation, destroying the mitochondria and thus inducing cancer cells apoptosis. The targeted subcellular mitochondrial CO delivery combined with inhibitory HDAC activity maximized the cytotoxicity of the nanoplatform which may provide new insights for CO-mediated multimodal therapies for cancer treatment.

The longitudinal risk of mortality between invasive ductal carcinoma and metaplastic breast carcinoma.

The management of metaplastic breast carcinoma (MBC) has largely paralleled the paradigms used for invasive ductal carcinoma (IDC) in the current National Comprehensive Cancer Network guidelines of breast cancer. However, patients with IDC and MBC have been shown to have a different prognosis, and there are significant differences in risk and failure patterns after treatment. The purpose of this study was to compare breast cancer specific survival (BCSS) and hazard function between IDC and MBC. We included patients from the Surveillance, Epidemiology, and End Results program with stage I-III IDC and MBC between 2000 and 2012. Statistical analyses were including chi-square analysis, life-table methods, multivariate Cox proportional hazards models, and propensity score matching (PSM). We identified 294,719 patients; 293,199 patients with IDC and 1520 patients with MBC. Multivariate analyses showed that the MBC subtype had significantly lower BCSS than the IDC subtype before and after PSM (p < 0.001). There were significant differences in the hazard curve between IDC and MBC. The hazard curve for breast cancer mortality in the IDC cohort peaked at 3 years (2%), and then changed to a slowly decreasing plateau after prolonged follow up. However, the hazard curve for breast cancer mortality in the MBC cohort peaked at 2 years (7%), then declined sharply between 3 and 6 years, and changed to a low death rate after a follow-up time exceeding 6 years. Subgroup analyses revealed that the hazard curves significantly differed between IDC and MBC after stratifying by tumor stage and hormone receptor status. Our study suggests that patients with MBC should receive more effective systemic agents and intensive follow-up because of their significantly augmented risk of death compared to IDC patients.

GelFAP: Gene Functional Analysis Platform for Gastrodia elata.

Gastrodia elata, also named Tianma, is a valuable traditional Chinese herbal medicine. It has numerous important pharmacological roles such as in sedation and lowering blood pressure and as anticonvulsant and anti-aging, and it also has effects on the immune and cardiovascular systems. The whole genome sequencing of G. elata has been completed in recent years, which provides a strong support for the construction of the G. elata gene functional analysis platform. Therefore, in our research, we collected and processed 39 transcriptome data of G. elata and constructed the G. elata gene co-expression networks, then we identified functional modules by the weighted correlation network analysis (WGCNA) package. Furthermore, gene families of G. elata were identified by tools including HMMER, iTAK, PfamScan, and InParanoid. Finally, we constructed a gene functional analysis platform for G. elata . In our platform, we introduced functional analysis tools such as BLAST, gene set enrichment analysis (GSEA), and cis-elements (motif) enrichment analysis tool. In addition, we analyzed the co-expression relationship of genes which might participate in the biosynthesis of gastrodin and predicted 19 mannose-binding lectin antifungal proteins of G. elata. We also introduced the usage of the G. elata gene function analysis platform (GelFAP) by analyzing CYP51G1 and GFAP4 genes. Our platform GelFAP may help researchers to explore the gene function of G. elata and make novel discoveries about key genes involved in the biological processes of gastrodin.

Self-Amplified Apoptosis Targeting Nanoplatform for Synergistic Magnetic-Thermal/Chemo Therapy In Vivo.

The low efficiency homing of nanomaterials in tumors remains a major challenge in nanomedicine. Inspired by the apoptosis targeting properties of phosphatidylserine (PS), a self-amplified apoptosis targeting nanoplatform (MNPs-ZnDPA/ß-Lap) is fabricated combining Zn0.4 Co0.6 Fe2 O4 @Zn0.4 Mn0.6 Fe2 O4 nanoparticles (MNPs) with an excellent magnetic hyperthermia effect, a chemotherapeutic drug of ß-lapachone (ß-Lap) with the promotion of cell apoptosis, and the good apoptosis targeting moiety of Zn(II)-bis(dipicolylamine) (bis-ZnDPA) for PS. In an apoptotic 4T1 xenograft model, MNPs-ZnDPA/ß-Lap can first accumulate in tumors by the EPR effect. The released ß-Lap triggers the apoptosis of cancer cells in the tumor and increases the apoptotic target, which results in amplifying their apoptosis targeting properties. This self-amplified apoptosis targeting efficiency of MNPs-ZnDPA/ß-Lap almost inhibits the growth of tumors with the synergistic magnetic-thermal/chemo therapy, which can offer a significant promise for targeting cancer theranostics.

Magnetic-Photoacoustic Dual-Mode Probe for the Visualization of H2S in Colorectal Cancer.

Techniques for the qualitative and quantitative detection of H2S in vivo have attracted considerable attention due to the key role of H2S in various physiological and pathological processes. However, in vivo detection strategies for H2S are mainly based on fluorescence imaging, which is limited by its poor tissue penetration. Moreover, the limitations of single-mode probes are amplified in complex physiological environments. Herein, a core-shell Fe3O4@Cu2O nanoparticle was constructed as a magnetic-photoacoustic dual-mode probe for H2S detection in vitro and in vivo based on the in situ response of Cu2O to endogenous H2S in colon tumors. This probe is expected to greatly improve the accuracy of H2S detection in vivo because it employs two detection methods with complementary advantages. The new probe was experimentally applied to the in vivo and in vitro visualization of H2S in mice with colorectal cancer, validating the in situ reaction-activated dual-detection method. This work establishes a simple and efficient dual-mode imaging method based on a novel trigger mechanism. The findings provide a new strategy for colon cancer detection based on the in situ reactions at tumor sites.

A smart theranostic platform for photoacoustic and magnetic resonance dual-imaging-guided photothermal-enhanced chemodynamic therapy.

The use of smart theranostic agents in multimodal imaging and treatment is a promising strategy to overcome the limitations of single mode diagnosis and treatment, and can greatly improve the diagnosis and effects of treatment. In this study, a gold@manganese dioxide (Au@MnO2) core-shell nanostructure was designed as a glutathione (GSH)-triggered smart theranostic agent for photoacoustic and magnetic resonance (MR) dual-imaging-guided photothermal-enhanced chemodynamic therapy. Both in vitro and in vivo experiments demonstrated not only that the photoacoustic and MR imaging function of Au@MnO2 could be activated by a high endogenous GSH concentration, but also that after being triggered by the endogenous GSH, Au@MnO2 had an excellent synergistic treatment effect in photothermal-enhanced chemodynamic therapy under the guidance of photoacoustic and MR imaging. This study demonstrated that the use of GSH-triggered Au@MnO2 in photoacoustic and MR dual-imaging-guided photothermal-enhanced chemodynamic therapy is a smart theranostic nanoplatform for the accurate diagnosis and efficient treatment of cancer.

pH and Glutathione Synergistically Triggered Release and Self-Assembly of Au Nanospheres for Tumor Theranostics.

Theranostic agents based on near-infrared absorption which integrate both imaging and therapeutic functions have attracted considerable attention. However, because of the interference signal, indiscriminate treatment usually causes side effects on normal tissues during tumor treatment. To address this limitation, we propose a new synergistically triggered mechanism, release and self-assembly of Au nanospheres, for tumor theranostics based on the synergistic effect of H+ and glutathione on the tumor microenvironment. In vitro experiments reveal that Au nanospheres release from Au@ZIF-8 at a high concentration of H+ or glutathione. Importantly, Au aggregation only appears in the synergistic effect of glutathione and lower pH and exhibits strong coupling plasmonic resonance absorption in the near-infrared region and can be used as the theranostics agent. This statement was further verified by biological transmission electron microscopy and in vivo imaging. Au@ZIF-8 is stable and produces no photoacoustic signal in normal tissue; in contrast, in the presence of overexpressed glutathione and H+, Au nanospheres release from Au@ZIF-8, assemble to aggregates, and exhibit a strong signal at the tumor site for imaging and efficient photothermal therapy. This work provides a new strategy for designing theranostic agents with sequentially responsive steps to avoid interference diagnosis signals from normal tissues and reduce damage to normal tissue during treatment.

Mn-Porphyrin-Based Metal-Organic Framework with High Longitudinal Relaxivity for Magnetic Resonance Imaging Guidance and Oxygen Self-Supplementing Photodynamic Therapy.

A nanoplatform for magnetic resonance imaging guidance and oxygen self-supplementing photodynamic therapy (PDT) was constructed on the basis of a porous metal-organic framework (PCN-222(Mn)), which was built by simple Mn-porphyrin ligands and biocompatible Zr4+ ions. Because of the good dispersibility of Mn3+ in the open framework and the high water affinity of the channel, PCN-222(Mn) exhibits a high longitudinal relaxivity of ∼35.3 mM-1 s-1 (1.0 T). In addition, it shows good catalytic activity for the conversion of endogenous hydrogen peroxide into oxygen, thereby improving tumor hypoxia during photodynamic therapy. The intravenous injection of PCN-222(Mn) into tumor-bearing mice mode provided good T1-weighted contrast of the tumor site and effectively inhibited tumor growth upon a single-laser irradiation. The findings provide insights for the development of multifunctional theranostic nanoplatforms based on simple components.

An Optical/Photoacoustic Dual-Modality Probe: Ratiometric in/ex Vivo Imaging for Stimulated H2S Upregulation in Mice.

Tracking signaling H2S in live mice demands responsive imaging with fine tissue imaging depth and low interferences from tissue scattering/autofluorescence and probe concentration. With complementary advantages of fluorescence and photoacoustic (PA) imaging, optical/PA dual-modality imaging was suggested for in/ex vivo H2S imaging. Therefore, a meso-benzoyloxyltricarboheptamethine cyanine, HS-CyBz, was prepared as the first ratiometric optical/PA dual-modality probe for H2S, profiting from a keto-enol transition sensing mechanism. Tail intravenous injection of this probe leads to probe accumulation in the liver of mice, and the endogenous H2S upregulation triggered by S-adenosyl-l-methionine has been verified by ratiometric optical/PA imaging, suggesting the promising potential of this ratiometric dual-modality imaging.

Surface Plasmon Resonance-Enhanced Photoacoustic Imaging and Photothermal Therapy of Endogenous H2 S-Triggered Au@Cu2 O.

Smart theranostics agents triggered by endogenous H2 S with combined activated photoacoustic imaging and photothermal therapy can improve the diagnosis and treatment of colon cancer. However, the low theranostic performance of the current smart theranostics agents after the triggering step has limited their further application. In this work, the theranostic performance of endogenous H2 S-triggered Au@Cu2 O for the diagnosis and treatment of colon cancer, which is generated from the localized surface plasmon resonance coupling effect between a noble metal (Au) and a semiconductor (Cu2 O), is investigated. Compared with Cu2 O, the prepared H2 S-triggered Au@Cu2 O shows a significantly stronger absorption at the near-infrared region, such as a ≈2.1 times change at 808 nm, giving a photothermal conversion efficiency increase of ≈1.2 times. More importantly, Au@Cu2 O still exhibits good photoacoustic imaging contrast and photothermal properties for treatment of colon cancer in vivo even at very low injection doses. This work not only investigates an endogenous H2 S-triggered Au@Cu2 O theranostic agent with enhanced theranostic performance for colon cancer but also provides a novel strategy for designing high-performance theranostic agents.

Tumor pH-Responsive Albumin/Polyaniline Assemblies for Amplified Photoacoustic Imaging and Augmented Photothermal Therapy.

Tumor-microenvironment-responsive theranostics have great potential for precision diagnosis and effective treatment of cancer. Polyaniline (PANI) is the first reported pH-responsive organic photothermal agent and is widely used as a theranostic agent. However, tumor pH-responsive PANI-based theranostic agents are not explored, mainly because the conversion from the emeraldine base (EB) to emeraldine salt (ES) state of PANI requires pH < 4, which is lower than tumor acidic microenvironment. Herein, a tumor pH-responsive PANI-based theranostic agent is designed and prepared for amplified photoacoustic imaging guided augmented photothermal therapy (PTT), through intermolecular acid-base reactions between carboxyl groups of bovine serum albumin (BSA) and imine moieties of PANI. The albumin/PANI assemblies (BSA-PANI) can convert from the EB to ES state at pH < 7, accompanied by the absorbance redshift from visible to near-infrared region. Both in vitro and in vivo results demonstrate that tumor acidic microenvironment can trigger both the photoacoustic imaging (PAI) signal amplification and the PTT efficacy enhancement of BSA-PANI assemblies. This work not only highlights that BSA-PANI assemblies overcome the limitation of low-pH protonation, but also provides a facile assembly strategy for a tumor pH-responsive PANI-based nanoplatform for cancer theranostics.

Macrophages-Mediated Delivery of Small Gold Nanorods for Tumor Hypoxia Photoacoustic Imaging and Enhanced Photothermal Therapy.

Macrophage-mediated delivery of drugs or nanoparticles has great potential in cancer treatment because it can avoid interception by the immune system and cross the blood-vessel barriers to reach the hypoxic regions of tumors. However, macrophage-based delivery system still faces some great challenges such as low theranostics agent loading capacity and hypoxic regions tendency in vivo. Herein, small gold nanorods (AuNRs) were used as the model theranostics agent to design a macrophage-mediated delivery system with high loading quantity for tumor hypoxia photoacoustic (PA) imaging and enhanced photothermal therapy (PTT). AuNRs modified with various thiolated poly(ethylene glycol)s (HS-PEG) via ligand exchange were investigated for toxicity and cell uptake by macrophages. The tumor hypoxic regions tendency of macrophage-loaded Anionic-AuNRs (Anionic-AuNRs@RAW) were verified by in vivo PA imaging and tumor sections. In vivo systemic PTT demonstrated enhanced tumor inhibition of anionic-AuNRs@RAW. This macrophage-mediated delivery system with high loading capacity could be used to enhance the effectiveness of cancer treatment.

Targeted and NIR light-controlled delivery of nitric oxide combined with a platinum(iv) prodrug for enhanced anticancer therapy.

This study reports a strategy of combining a Pt(iv) prodrug and a ruthenium nitrosyl (Ru-NO) donor into a single nanoplatform {N-GQDs@Ru-NO-Pt@FA} in which the platinum(iv) prodrug is conjugated onto a photoactivatable NO donor (Ru-NO) through a covalent bond and the nitric oxide-releasing platinum prodrug and folate groups are decorated on N-doped graphene quantum dots (N-GQDs). After cellular uptake of the nanoplatform, the platinum(iv) prodrug was reduced to an active anti-cancer Pt(ii) species inside the cancerous cells, and simultaneously, near-infrared (NIR) light illumination induced the release of NO, accompanied by a prominent photothermal effect. This nanoplatform is capable of targeting intracellular co-delivery of Pt(ii) and NO under 808 nm NIR light irradiation, accompanied by photothermal therapy, thereby leading to a significant synergistic therapeutic effect.

Ultrasmall WO3- x@γ-poly-l-glutamic Acid Nanoparticles as a Photoacoustic Imaging and Effective Photothermal-Enhanced Chemodynamic Therapy Agent for Cancer.

Synergistic treatment strategies for cancer have attracted increasing attention owing to their enhanced therapeutic effects compared with monotherapy. Chemodynamic therapy (CDT) is an emerging and thriving in situ treatment for cancer owing to its high regioselectivity and activation only by endogenous substances. However, the therapeutic effects of CDT are hindered by low reaction speeds. Here, ultrasmall WO3- x@γ-poly-l-glutamic acid (WO3- x@γ-PGA) nanoparticles (NPs) with good photoacoustic and photothermal properties were prepared, and their chemodynamic performance based on a Fenton-like reaction was explored due to its good catalytic effect. The synergistic treatment effect was also investigated by photothermal-enhanced CDT based on single WO3- x@γ-PGA NPs using a penetrating near-infrared-II laser both in vitro and in vivo. This work provides an effective treatment for cancer and further develops the CDT.

Fucoidan Extracted from Undaria pinnatifida: Source for Nutraceuticals/Functional Foods.

The importance of fucoidan as a functional ingredient in food, health products, and pharmaceutics is well-recognized due to its beneficial biological effects. Fucoidan is usually extracted from brown seaweeds, including Undaria pinnatifida. Fucoidan exhibits beneficial bio-activity and has antioxidant, anticancer, and anticoagulant properties. This review focuses on the biological activity of U. pinnatifida-derived fucoidan and investigates its structure⁻activity or fraction⁻activity relationship. It also describes several fucoidan extracts, along with their claimed anticancer effects. It aims to provide information and thoughts for future research such as the development of fucoidan into functional foods or nutraceuticals.

Concentration effect on large scale synthesis of high quality small gold nanorods and their potential role in cancer theranostics.

Cancer theranostics agents, such as gold nanorods, represent great potential in cancer therapy. However, the big size and the low yield of the gold nanorods reported previously have limited their clinical translation. Therefore, it is significant to develop a new method to prepare the small gold nanorods (width <8 nm) at larger scale. In this report, a modified seedless method was proposed based on the effect of precursor concentration assisted synthesis of high quality small gold nanorods at large scale. The obtained small gold nanorods exhibit high quality and dimension of (18 ±â€¯5 nm) × (5 ±â€¯1 nm). After modified with biological compatibility reagents, the small gold nanorods behave excellent photoacoustic imaging and photo-thermal therapy ability. These results manifest that the obtained small gold nanorods not only realize the improvements of previously limitations, also are thus supposed to pave the way to cancer theranostics in clinic application.

Functionalized Cu3BiS3 nanoparticles for dual-modal imaging and targeted photothermal/photodynamic therapy.

Multifunctional nano-biomaterials with the integration of diagnostic and therapeutic functions have shown great promise in improving the efficacy of cancer therapy. Herein, a new nanoplatform based on functionalized Cu3BiS3 nanoparticles (NPs) is fabricated for tumour-targeted combination phototherapy. The as-synthesized hydrophobic Cu3BiS3 NPs are modified with DSPE-PEG/DSPE-PEG-NH2, followed by the conjugation of the photosensitizer chlorin e6 (Ce6) and the target ligand folic acid (FA). The introduced Ce6 can further form a chelate complex with Gd3+. The rationally designed Cu3BiS3-PEG-(Ce6-Gd3+)-FA NPs, which have high physiological stability and good biocompatibility, can specifically target FA-receptor over-expressed tumour cells. The Cu3BiS3-PEG-(Ce6-Gd3+)-FA NPs exhibit effective dual-modal CT and MR imaging in the xenografted HeLa tumours. Importantly, excellent in vivo anti-tumour effects have been achieved by synergistic photothermal/photodynamic therapy using the multifunctional NPs. We expect that this versatile nanoplatform will play a role in exploring precise cancer diagnosis and therapy.

Photoacoustic-Enabled Self-Guidance in Magnetic-Hyperthermia Fe@Fe3 O4 Nanoparticles for Theranostics In Vivo.

Magnetic nanoparticles have gained much interest for theranostics benefited from their intrinsic integration of imaging and therapeutic abilities. Herein, c(RGDyK) peptide PEGylated Fe@Fe3 O4 nanoparticles (RGD-PEG-MNPs) are developed for photoacoustic (PA)-enabled self-guidance in tumor-targeting magnetic hyperthermia therapy in vivo. In the αv ß3 -positive U87MG glioblastoma xenograft model, the PA signal of RGD-PEG-MNPs reaches its maximum in the tumor at 6 h after intravenous administration. This signal is enhanced by 2.2-folds compared to that of the preinjection and is also 2.2 times higher than that in the blocking group. It demonstrates the excellent targeting property of RGD-PEG-MNPs. With the guidance of the PA, an effective magnetic hyperthermia to tumor is achieved using RGD-PEG-MNPs.