Reconciling the conflicting needs for a prolonged circulation time, enhanced cellular uptake by bulk tumor cells and cancer stem cells (CSCs), and extensive tumor tissue penetration remains a major challenge for current nano drug delivery systems. Here we describe smart poly­(N-isopropylacrylamide)-based nanogels with a fast adaptive hydrophobicity to solve these contradictory requirements for enhanced cancer chemotherapy. The nanogels are hydrophilic in the blood to prolong their circulation time. Once they accumulate at tumor sites, they rapidly become hydrophobic in response to tumor extracellular acidity. The adaptive hydrophobicity of the nanogels facilitates tumor accumulation, deep tumor penetration, and efficient uptake by bulk tumor cells and CSCs, resulting in a greater in vivo enrichment in tumor cells and side population cells. Together with lysosomal pH-regulated charge reversal and redox-responsive intracellular drug release, the nanogels escape from lysosomes and release their cargo doxorubicin. Thus, the nanogels significantly improve the in vivo anticancer efficacy and decrease side effects of doxorubicin. Strikingly, the ratio of CSCs is greatly decreased after treatment with the nanogels loaded with doxorubicin. Our current study provides new insights into designing effective anticancer drug delivery systems.

Low vaccine immunogenicity and tumor heterogenicity greatly limit the therapeutic effect of tumor vaccine. In this study, a novel injectable adhesive hydrogel, based on thermosensitive nanogels containing catechol groups and loaded with in situ‐forming MnO2 nanoparticles, is constructed to overcome these issues. The concentrated nanogel dispersion transforms into an adhesive hydrogel in situ after intratumoral injection. The photothermal effect of the loaded MnO2 nanoparticles induces immunogenic cell death to release mass autologous tumor‐derived protein antigens under near‐infrared irradiation, which act as ideal immune stimulating substances avoiding the problem of tumor heterogenicity and are captured by the in situ‐forming adhesive hydrogel. The antigens‐captured adhesive hydrogel acts as an “antigen reservoir” and releases these captured antigens to recruit more dendritic cells to stimulate an intensive and lasting anti‐tumor immune response mediated by CD8+ T cells. The primary tumors can be almost completely disappeared within 4 days without relapse, and the growth of the distal tumors and rechallenged tumors are also effectively inhibited by the treatment with the injectable adhesive hydrogel‐based photothermal therapy. Therefore, the proposed “antigen reservoir” strategy shows the great potential application as an in situ‐forming personalized vaccine to enhancing the cancer immune therapy.

Rationale: Immune checkpoint (ICP) blockade therapy combined with chemotherapy is a promising treatment strategy for tumors. Chemotherapeutic agents usually function inside the tumor cells, while ICP inhibitors are efficacious out of the tumor cells. It is desirable to effectively co-deliver an ICP inhibitor and a chemotherapy agent to different sites of a tumor. We have designed an effective drug delivery system to accomplish both objectives. Methods: We designed a Pickering nanoemulsion (PNE) using multi-sensitive nanogels with pH-responsive, hydrophilicity-hydrophobicity switch, and redox-responding properties as an oil/water interfacial stabilizer. The D/HY@PNE was employed for specified spatial delivery of the chemotherapy agent doxorubicin (DOX) and ICP inhibitor HY19991 (HY). We systematically investigated the pH-responsive disassembly of PNE, the release of DOX and HY from D/HY@PNE in the tumor microenvironment, enhanced tumor penetration of DOX, immunogenic cell death (ICD), antitumor efficacy, and the immune response induced by D/HY@PNE in vitro and in vivo . Results: D/HY@PNE disassembled to release the ICP inhibitor HY and DOX-loaded nanogels due to the hydrophilicity-hydrophobicity reversal of nanogels in the acidic tumor microenvironment. Quantitative analysis indicates that D/HY@PNE presents enhanced tumor penetration behavior and effectively induces ICD. The strong immune response induced by D/HY@PNE was due to the efficient synergetic combination of chemotherapy and immunotherapy and resulted in enhanced antitumor efficacy in 4T1 tumor-bearing mice. Conclusion: This novel strategy highlights the promising potential of a universal platform to co-deliver different therapeutic or diagnostic reagents with spatial regulation to improve the anti-tumor effect.

Injectable hydrogels have been developed as biomedical materials in various fields but the biofouling on their surface limits the applications in vivo. In this work, zwitterionic structure was introduced into...

In the era of Corona Virus Disease 2019 (COVID-19), inappropriate indoor ventilation may turn out to be the culprit of microbial contamination in enclosed spaces and deteriorate the environment. To collaboratively improve the thermal comfort, air quality and virus spread control effect, it was essential to have an overall understanding of different ventilation modes. Hence, this study reviewed the latest scientific literature on indoor ventilation modes and manuals of various countries, identified characteristics of different ventilation modes and evaluated effects in different application occasions, wherefore to further propose their main limitations and solutions in the epidemic era. For thermal comfort, various non-uniform ventilation modes could decrease the floor-to-ceiling temperature difference, draft rate or PPD by 60%, 80% or 33% respectively, or increase the PMV by 45%. Unsteady ventilation modes (including intermittent ventilation and pulsating ventilation) could lower PPD values by 12%–37.8%. While for air quality and virus spread control, non-uniform ventilation modes could lower the mean age of air or contaminants concentration by 28.3%–47% or 15%–47% respectively, increase the air change efficiency, contaminant removal effectiveness or protection efficiency by 6.6%–10.4%, 22.6% or 14%–50% respectively. Unsteady ventilation mode (pulsating ventilation) could reduce the peak pollutant concentration and exposure time to undesirable concentrations by 31% and 48% respectively. Non-uniform modes and unsteady modes presented better performance in thermal comfort, air quality and virus spread control, whereas relevant performance evaluation indexes were still imperfect and the application scenarios were also limited.

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