Nanodrug regulates lactic acid metabolism to reprogram the immunosuppressive tumor microenvironment for enhanced cancer immunotherapy.

A majority of cancers fail to respond to immunotherapy due to the immunosuppressive tumor microenvironment (TME), and metabolic regulation of the TME has been a promising strategy to improve immunotherapy. Lactate is a key metabolic player in tumor immune response since its excess secretion aggravates tumor immune escape by favoring the polarization of tumor-associated macrophages (TAMs) to an immunosuppressive phenotype meanwhile impeding the tumor infiltration of the cytotoxic T lymphocyte. Here, we proposed a metabolic reprogramming mechanism to ameliorate tumor immunosuppression by using lonidamine and syrosingopine incorporated liposomes (L@S/L) to regulate lactate production and efflux. Concretely, lonidamine reduced lactate production by affecting the glycolytic metabolic pathway while syrosingopine decreased lactate efflux by inhibiting the key protein expression of the lactate transporter MCT-4. Consequently, both the drugs synergistically normalize the pH of the TME to overcome the tumor immunosuppressive microenvironment. In vivo studies demonstrated that the decreased extracellular lactate preferentially polarized TAMs to the M1 phenotype, simultaneously increased the proportion of NK cells and reduced the number of Treg cells. These results validated an efficient tumor immunotherapy in the breast cancer model. This new strategy of lactic acid metabolism regulation is proposed to operate in concert with immune modulation in the TME, which shows great potential for immunotherapy of immunologically "cold" tumors.

COCu: A Robust Self-Regenerative Hydrogel with Applicability as Both Hydrated Gel Dressing and Dry Suture for Seamless Tissue Fixation and Repair.

Self-regenerative hydrogels have recently been developed, and represent a special type of self-healing hydrogels with the ability to restore a dehydrated hydrogel with physical damage. In this study, a self-regenerative hydrogel (COCu) based on two chitosan polymers assembled by slow-released Cu2+ is developed. The COCu hydrogel displays an excellent regeneration ability after being dehydrated and fractured. By simple hydration at room temperature, the fragments of the dehydrated gel fuse into one seamless whole, thereby preserving the mechanical properties and functionalities of the original hydrogel. The regeneration process can be conducted repeatedly after different methods of dehydration (natural volatilization, heat drying, lyophilization) and various modes of deconstruction (flakes, powder, lumpy sponge, etc.). Furthermore, the COCu hydrogel provides ultra-stretchability, and it can be stretched into thin (0.01-0.1 mm) filaments, which, when dried (dtCOCu), can be used as suture lines. Moreover, when used as a dry suture, it regenerates into the hydrogel in the presence of the tissue fluid, forming an excellent sealant to immobilize tissues and seamlessly seal wounds. The fast self-regeneration allows for its facile application as both a hydrated gel dressing and dry suture, and offers customized strategies for fixing and repair of different wounds in soft tissues.

One-step removal of harmful algal blooms by dual-functional flocculant based on self-branched chitosan integrated with flotation function.

Harmful algal blooms induce severe environmental problems. It is challenging to remove algae by the current available treatments involving complicate process and costly instruments. Here, we developed a CaO2@PEG-loaded water-soluble self-branched chitosan (CP-SBC) system, which can remove algae from water in one-step without additional instrumentation. This approach utilizes a novel flocculant (self-branched chitosan) integrated with flotation function (induced by CaO2@PEG). CP-SBC exhibited better flocculation performance than commercial flocculants, which is attributed to the enhanced bridging and sweeping effect of branched chitosan. CP-SBC demonstrated outstanding biocompatibility, which was verified by zebrafish test and algae activity test. CaO2@PEG-loaded self-branched chitosan can serve as an "Air flotation system" to spontaneous float the flocs after flocculation by sustainably released O2. Furthermore, CP-SBC can improve water quality through minimizing dissolved oxygen depletion and reducing total phosphorus concentrations.

Transparent floatable magnetic alginate sphere used as photocatalysts carrier for improving photocatalytic efficiency and recycling convenience.

Practical application of powder photocatalysts is far from satisfying due to their low photon utilization, inconvenient recovery and potential environmental risk. In this study, an easily recoverable, environmentally friendly and highly transparent floatable magnetic photocatalyst carrier was prepared based on biopolymer alginate and Fe3O4 particles. Further, three different types of photocatalysts were chosen as model semiconductor photocatalysts and loaded on the shell of the carriers. The freeze process facilitated the formation of internal cavities that enhanced floating ability and transparency of the spheres. Meanwhile, the excellent floating performance offered massive reaction sites for pollutants reacting with photocatalysts, O2 and photons on the air/water interface. Photodegradation results showed all three floatable hybrid photocatalysts exhibited enhanced photocatalytic efficiencies compared to the virgin photocatalysts. In short, the carrier can integrate excellent floating ability, environmental friendliness and full recycling with good stability, and it can greatly improve the photocatalytic efficiency of various powder semiconductor photocatalysts.