NIR-dye bridged human serum albumin reassemblies for effective photothermal therapy of tumor.

Human serum albumin (HSA) based drug delivery platforms that feature desirable biocompatibility and pharmacokinetic property are rapidly developed for tumor-targeted drug delivery. Even though various HSA-based platforms have been established, it is still of great significance to develop more efficient preparation technology to broaden the therapeutic applications of HSA-based nano-carriers. Here we report a bridging strategy that unfastens HSA to polypeptide chains and subsequently crosslinks these chains by a bridge-like molecule (BPY-Mal2) to afford the HSA reassemblies formulation (BPY@HSA) with enhanced loading capacity, endowing the BPY@HSA with uniformed size, high photothermal efficacy, and favorable therapeutic features. Both in vitro and in vivo studies demonstrate that the BPY@HSA presents higher delivery efficacy and more prominent photothermal therapeutic performance than that of the conventionally prepared formulation. The feasibility in preparation, stability, high photothermal conversion efficacy, and biocompatibility of BPY@HSA may facilitate it as an efficient photothermal agents (PTAs) for tumor photothermal therapy (PTT). This work provides a facile strategy to enhance the loading capacity of HSA-based crosslinking platforms in order to improve delivery efficacy and therapeutic effect.

Microbial synthesis of Prussian blue for potentiating checkpoint blockade immunotherapy.

Cancer immunotherapy is revolutionizing oncology. The marriage of nanotechnology and immunotherapy offers a great opportunity to amplify antitumor immune response in a safe and effective manner. Here, electrochemically active Shewanella oneidensis MR-1 can be applied to produce FDA-approved Prussian blue nanoparticles on a large-scale. We present a mitochondria-targeting nanoplatform, MiBaMc, which consists of Prussian blue decorated bacteria membrane fragments having further modifications with chlorin e6 and triphenylphosphine. We find that MiBaMc specifically targets mitochondria and induces amplified photo-damages and immunogenic cell death of tumor cells under light irradiation. The released tumor antigens subsequently promote the maturation of dendritic cells in tumor-draining lymph nodes, eliciting T cell-mediated immune response. In two tumor-bearing mouse models using female mice, MiBaMc triggered phototherapy synergizes with anti-PDL1 blocking antibody for enhanced tumor inhibition. Collectively, the present study demonstrates biological precipitation synthetic strategy of targeted nanoparticles holds great potential for the preparation of microbial membrane-based nanoplatforms to boost antitumor immunity.

Dual Gate-Controlled Therapeutics for Overcoming Bacterium-Induced Drug Resistance and Potentiating Cancer Immunotherapy.

The presence of bacteria in the tumor can cause cancer resistance to chemotherapeutics. To fight against bacterium-induced drug resistance, herein we design self-traceable nanoreservoirs that are simultaneously loaded with gemcitabine (an anticancer drug) and ciprofloxacin (an antibiotic) and are decorated with hyaluronic acid for active tumor targeting. The nanoreservoirs have a pH-sensitive gate and an enzyme-responsive gate that can be opened in the acidic and hyaluronidase-abundant tumor microenvironment to control drug release rates. Moreover, the nanoreservoirs can specifically target the tumor regions without eliciting evident toxicity to normal tissues, kill the intratumoral bacteria, and inhibit the tumor growth even in the presence of the bacteria. Unexpectedly, the nanoreservoirs can activate T cell-mediated immune responses through promoting antigen-presenting dendritic cell maturation and depleting immunosuppressive myeloid-derived suppressor cells in bacterium-infected tumors.

A conjugated-polymer-based ratiometric nanoprobe for evaluating in-vivo hepatotoxicity induced by herbal medicine via MSOT imaging.

Herbal medicines are widely used around the world, while some of them are associated with adverse effects like herb-induced liver injury due to oxidative/nitrosative stress resulted from hepatically-generated ROS/RNS. It is of significance to accurately evaluate herbal-medicine-induced hepatotoxicity, since it would help provide effective monitoring method of the safety of herbal remedies. Herein we designed a ratiometric nanoprobe for in vivo imaging hepatic injury induced by herbal medicine (polygonum multiflorum, PM) via specifically responding to NO generated in liver by PM, and with MSOT imaging the precise location of liver injury can be identified. The liposomal nanoprobe consists of a responsive dye (IX-2NH2) which could specifically respond to NO and the diketopyrrolopyrrole-based conjugated polymer (DPP-TT) as the internal reference. Thus we can realize ratiometric optoacoustic detection of herbal-medicine-induced liver injury with 3D information in mouse model in a noninvasive way.

Effects of dietary oxidized konjac glucomannan sulfates (OKGMS) and acidolysis-oxidized konjac glucomannan (A-OKGM) on the immunity and expression of immune-related genes of Schizothorax prenanti.

In the present study, konjac glucomannan (KGM) was degraded by H2O2, and then used trisulfonated sodium amine and HCl, individually, to obtain two kinds of derivatives: oxidized konjac glucomannan sulfates (OKGMS) and acidolysis-oxidized konjac glucomannan (A-OKGM). The effects of two OKGM modified products on the immune parameters and expressions of toll-like receptor 22 (TLR22), myeloid differentiation factor 88 (MyD88) and interferon regulatory factors 7 (IRF7) genes in Schizothorax prenanti were determined. The alternative haemolytic complement (ACH50) activity was found to be significantly increased by the OKGMS diets. The immunoglobulin M (IgM) level was significantly enhanced by the OKGMS diets. The lysozyme activity was significantly increased by both OKGMS and A-OKGM diets. The superoxide dismutase (T-SOD) activity in fish fed with all doses of OKGMS diets was significantly higher than that in fish fed with basal diet. The glutathione peroxidase (GSH-PX) activity in fish fed with 0.8% and 1.6% A-OKGM diets was significantly higher than control group. The malondialdehyde (MDA) level was significantly decreased by both OKGMS and A-OKGM diets. The 0.8% A-OKGM diet significantly up-regulated TLR22 gene expression in the head kidney and spleen. TLR22 gene expression was significantly promoted by all OKGMS diets in the mesonephros and liver. The MyD88 mRNA level in 1.6% A-OKGM group significantly increased in the head kidney. The low dose of OKGMS significantly induced the MyD88 gene expression in the mesonephros, gut and liver, while 0.8% A-OKGM group also showed a significantly enhanced MyD88 mRNA expression in the gut. High dose of OKGMS significantly increased the IRF7 mRNA expression in the mesonephros and spleen. Fish fed with low dose of A-OKGM showed significantly higher expression of IRF7 in the gut and liver. Present study suggested that OKGMS and A-OKGM can act as immunostimulant to improve the immune indexes and up-regulate the immune-related gene expressions.

The effects of dietary oxidized konjac glucomannan and its acidolysis products on the immune response, expression of immune related genes and disease resistance of Schizothorax prenanti.

In the present study, KGM was degraded by H2O2 and HCl to obtain two products with different molecular weights: oxidized konjac glucomannan (OKGM, 4.7 × 10(5) Da) and low-molecular-weight oxidized konjac glucomannan (L-OKGM, 9.2 × 10(3) Da). The effects of the two OKGM products on IL-1ß, TNF-α, and TLR22 gene expression, and immune parameters and the resistance to Aeromonas hydrophila of Schizothorax prenanti were determined. The results showed that the lysozyme activity was significantly enhanced by the L-OKGM diets. The SOD activity was significantly increased by both OKGM and L-OKGM diets. The MDA level of fish fed the OKGM and L-OKGM diets was significantly lower than the control group. IL-1ß mRNA level in the spleen significantly increased in all L-OKGM fed groups. The 8.0 g kg(-1) L-OKGM diet also significantly up-regulated IL-1ß gene expression in the head kidney. In the gut, IL-1ß mRNA levels were significantly higher in fish fed with the 8.0 g kg(-1) OKGM and 16.0 g kg(-1) L-OKGM diets. The TNF-α mRNA level of L-OKGM group significantly increased in the spleen, head kidney and gut. High dosing of OKGM significantly up-regulated TNF-α transcription in the head kidney, while only the 8.0 g kg(-1) OKGM group showed significantly higher TNF-α mRNA expression in the mesonephros. Fish fed the L-OKGM diets showed significantly higher expression of TLR22 in the spleen, head kidney and mesonephros. After the injection of A. hydrophila, the 8.0 g kg(-1) L-OKGM group showed a significantly higher survival rate than did the control group. Present study suggests that OKGM and L-OKGM can up-regulate immune-related gene expression and enhance disease resistance in S. prenanti, and L-OKGM exhibits higher immunomodulatory activity.

Effects of Oxidized Konjac glucomannan (OKGM) on growth and immune function of Schizothorax prenanti.

Schizothorax prenanti is an important existemic commercial fish in River Yangtze. OKGM (Oxidized Konjac glucomannan) is a kind of polysaccharide oxidative degraded from KGM. Added 500, 1000, 2000, 4000, 8000 mg/kg OKGM into the diets of S. prenanti. After 60 days feeding trial, WGR (weight gain rate), SGR (specific growth rate), PER (protein efficiency ratio) of groups fed the diet with 8000 mg/kg OKGM was all significantly (P < 0.05) higher; FCR (feed conversion ratio) was significantly lower than the control group whose diet have no OKGM. Hepatopancreas index, spleen index of group 6 whose feed added 8000 mg/kg OKGM were significantly higher and gallbladder index was significantly lower than the control group. Erythrocyte number, leukocyte number of group 5, 6 whose feed added 4000, 8000 mg/kg OKGM were excellent significantly (P < 0.01) more than the control group. At the same time, Erythrocyte phagocytic rate, erythrocyte phagocytic index, neutrophilic granulocyte phagocytic rate, neutrophilic granulocyte phagocytic index of all the groups whose diet added OKGM were significantly higher than the control group. Content of IgM, C3 of group 4 whose feed added 2000 mg/kg OKGM were significantly more than the control group. As for activity of CAT, group 6 was significantly higher than the control group. When compared activity of SOD, group 6 was significantly higher than group 1, 2, 3. Accordingly, activity of GSH-Px of group 3, 4, 5, 6 were significantly higher than the control group. On the contrary, content of MDA, group 3, 4, 5, 6 whose feed added 1000-8000 mg/kg OKGM was excellent significantly lower than the control group. After injected Aeromonas hydrophila 21 days, only group 6 whose feed added 8000 mg/kg OKGM survived excellent significantly more than the control group. So we can draw a conclusion of that added OKGM in the diets of S. prenanti, not only promoted growth, but also improved immune function, and the best dose was 8000 mg/kg in this experiment.