An oncolytic system produces oxygen selectively in pancreatic tumor cells to alleviate hypoxia and improve immune activation.

INTRODUCTION: Hypoxia is one of the important reasons for the poor therapeutic efficacy of current pancreatic cancer treatment, and the dense stroma of pancreatic cancer restricts the diffusion of oxygen within the tumor. METHODS: A responsive oxygen-self-supplying adv-miRT-CAT-KR (adv-MCK) cascade reaction system to improve hypoxia in pancreatic cancer is constructed. We utilized various experiments at multiple levels (cells, organoids, in vivo) to investigate its effect on pancreatic cancer and analyzed the role of immune microenvironment changes in it through high-throughput sequencing. RESULTS: The adv-MCK system is an oncolytic adenovirus system expressing three special components of genes. The microRNA (miRNA) targets (miRTs) enable adv-MCK to selectively replicate in pancreatic cancer cells. Catalase catalyzes the overexpressed hydrogen peroxide in pancreatic cancer cells to generate endogenous oxygen, which is catalyzed by killerRed to generate singlet oxygen (1O2) and further to enhance the oncolytic effect. Meanwhile, the adv-MCK system can specifically improve hypoxia in pancreatic cancer, exert antitumor effects in combination with photodynamic therapy, and activate antitumor immunity, especially by increasing the level of γδ T cells in the tumor microenvironment. CONCLUSION: The responsive oxygen-self-supplying adv-MCK cascade reaction system combined with photodynamic therapy can improve the hypoxic microenvironment of pancreatic cancer and enhance antitumor immunity, which provides a promising alternative treatment strategy for pancreatic cancer.

Three-in-One Oncolytic Adenovirus System Initiates a Synergetic Photodynamic Immunotherapy in Immune-Suppressive Cholangiocarcinoma.

Although photodynamic immunotherapy has been promoted in the clinical practice of cholangiocarcinoma, the insensitivity to photodynamic immunotherapy remains to be a great problem. This can be largely attributed to an immune-suppressive tumor microenvironment (TME) manifested as immature myeloid cells and exhausted cytotoxic T lymphocytes. Here, a three-in-one oncolytic adenovirus system PEG-PEI-Adv-Catalase-KillerRed (p-Adv-CAT-KR) has been constructed to multiply, initiate, and enhance immune responses in photodynamic immunotherapy, using genetically-engineered KillerRed as photosensitizer, catalase as in situ oxygen-supplying mediator, and adenovirus as immunostimulatory bio-reproducible carrier. Meanwhile, PEG-PEI is applied to protect adenovirus from circulating immune attack. The administration of p-Adv-CAT-KR induces increased antigen presenting cells, elevated T cell infiltrations, and reduced tumor burden. Further investigation into underlying mechanism indicates that hypoxia inducible factor 1 subunit alpha (Hif-1α) and its downstream PD-1/PD-L1 pathway contribute to the transformation of immune-suppressive TME in cholangiocarcinoma. Collectively, the combination of KillerRed, catalase, and adenovirus brings about multi-amplified antitumor photo-immunity and has the potential to be an effective immunotherapeutic strategy for cholangiocarcinoma.

Superhydrophobic/Superhydrophilic Janus Evaporator for Extreme High Salt-Resistance Solar Desalination by an Integrated 3D Printing Method.

The emerging solar desalination technology has incomparable advantages for providing a clean water solution. However, the issue of salt accumulation on the solar evaporator tops during the steam generation leads to a considerable decrease in the evaporation rate. Herein, we demonstrate a superhydrophobic/superhydrophilic Janus evaporator that enables a stable solar evaporation even in saturated brine. Our Janus solar evaporator with a superhydrophobic top and a superhydrophilic bottom has been manufactured integrally, allowing for a fast steam evaporation without the impediment of the accumulated salt residues. The superhydrophobic top changes the water passageway from the center toward the edges while it allows for the vertical transport of both solar thermo and evaporated steams. Salt residues would only be deposited at the edges of the superhydrophilic bottom, allowing for a long-term stability of the evaporator for a continuous (>50 h) solar evaporation in saturated brine, which is record-breaking for salt-resistant solar evaporators. With stable and efficient evaporation performance out of high-salinity brine, this work provides a fascinating avenue for the desalination of seawater in a salt-resistant and efficient manner.

Large-Scale, Abrasion-Resistant, and Solvent-Free Superhydrophobic Objects Fabricated by a Selective Laser Sintering 3D Printing Strategy.

Manufacturing abrasion-resistant superhydrophobic matters is challenging due to the fragile feature of the introduced micro-/nanoscale surface roughness. Besides the long-term durability, large scale at meter level, and 3D complex structures are of great importance for the superhydrophobic objects used across diverse industries. Here it is shown that abrasion-resistant, half-a-meter scaled superhydrophobic objects can be one-step realized by the selective laser sintering (SLS) 3D printing technology using hydrophobic-fumed-silica (HFS)/polymer composite grains. The HFS grains serve as the hydrophobic guests while the sintered polymeric network provides the mechanical strength, leading to low-adhesion, intrinsic superhydrophobic objects with desired 3D structures. It is found that as-printed structures remained anti-wetting capabilities even after undergoing different abrasion tests, including knife cutting test, rude file grinding test, 1000 cycles of sandpaper friction test, tape test and quicksand impacting test, illustrating their abrasion-resistant superhydrophobic stability. This strategy is applied to manufacture a shell of the unmanned aerial vehicle and an abrasion-resistant superhydrophobic shoe, showing the industrial customization of large-scale superhydrophobic objects. The findings thus provide insight for designing intrinsic superhydrophobic objects via the SLS 3D printing strategy that might find use in drag-reduce, anti-fouling, or other industrial fields in harsh operating environments.