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Immunogenic cell death (ICD), a dying state of the cells, encompasses the changes in the conformations of cell surface and the release of damage‐associated molecular patterns, which could initiate an adaptive immune response by stimulating the dendritic cells to present antigens to T cells. Advancements in biomaterials, nanomedicine, and micro‐ and nano‐technologies have facilitated the development of effective ICD inducers, but the potential toxicity of these vesicles encountered in drug delivery via intravenous administration hampers their further application. As alternatives, the local drug delivery systems have gained emerging attention due to their ability to prolong the retention of high payloads at the lesions, sequester drugs from harsh environments, overcome biological barriers to exert optimal efficacy, and minimize potential side effects to guarantee bio‐safety. Herein, a brief overview of the local drug delivery techniques used for ICD inducers is provided, explaining how these techniques broaden, alter, and enhance the therapeutic capability while circumventing systemic toxicity at the same time. The historical context and prominent examples of the local administration of ICD inducers are introduced. The complexities, potential pitfalls, and opportunities for local drug delivery techniques in cancer immunotherapy are also discussed. [ABSTRACT FROM AUTHOR]

Microneedles have been expected for the construction of next-generation biosensors towards personalization, digitization, and intellectualization due to their metrics of minimal invasiveness, high integration, and favorable biocompatibility. Herein, an overview of state-of-the-art microneedle-based detection and sensing systems is presented. First, the designs of microneedle devices based on extraction mechanisms are concluded, corresponding to different geometries and materials of microneedles. Second, the targets of equipment-assisted microneedle detections are summarized, as well as the objective significance, revealing the current performance and potential scenarios of these microneedles. Third, the trend towards highly integrated sensors is elaborated by emphasizing the sensing principles (colorimetric, fluorometric and electronic manner). Finally, the key challenges to be tackled and the perspectives on future development are discussed. [ABSTRACT FROM AUTHOR]

Due to its promising capacity in improving drug efficacy, polypharmacology has emerged to be a new theme in the drug discovery of complex disease. In the process of novel multi-target drugs (MTDs) discovery, in silico strategies come to be quite essential for the advantage of high throughput and low cost. However, current researchers mostly aim at typical closely related target pairs. Because of the intricate pathogenesis networks of complex diseases, many distantly related targets are found to play crucial role in synergistic treatment. Therefore, an innovational method to develop drugs which could simultaneously target distantly related target pairs is of utmost importance. At the same time, reducing the false discovery rate in the design of MTDs remains to be the daunting technological difficulty. In this research, effective small molecule clustering in the positive dataset, together with a putative negative dataset generation strategy, was adopted in the process of model constructions. Through comprehensive assessment on 10 target pairs with hierarchical similarity-levels, the proposed strategy turned out to reduce the false discovery rate successfully. Constructed model types with much smaller numbers of inhibitor molecules gained considerable yields and showed better false-hit controllability than before. To further evaluate the generalization ability, an in-depth assessment of high-throughput virtual screening on ChEMBL database was conducted. As a result, this novel strategy could hierarchically improve the enrichment factors for each target pair (especially for those distantly related/unrelated target pairs), corresponding to target pair similarity-levels. [ABSTRACT FROM AUTHOR]

Regulatory T (T reg ) cells underlie multiple autoimmune disorders and potentialize an anti-inflammation treatment with adoptive cell therapy. However, systemic delivery of cellular therapeutics often lacks tissue targeting and accumulation for localized autoimmune diseases. Besides, the instability and plasticity of T reg cells also induce phenotype transition and functional loss, impeding clinical translation. Here, we developed a perforated microneedle (PMN) with favorable mechanical performance and a spacious encapsulation cavity to support cell survival, as well as tunable channels to facilitate cell migration for local T reg therapy of psoriasis. In addition, the enzyme-degradable microneedle matrix could release fatty acid in the hyperinflammatory area of psoriasis, enhancing the T reg suppressive functions via the fatty acid oxidation (FAO)-mediated metabolic intervention. T reg cells administered through PMN substantially ameliorated psoriasis syndrome with the assistance of fatty acid-mediated metabolic intervention in a psoriasis mouse model. This tailorable PMN could offer a transformative platform for local cell therapy to treat a variety of diseases.