Search

Designing and developing photosensitizers with cell membrane specificity is crucial for achieving effective multimodal therapy of tumors compared to other organelles. Here, we designed and screened a photosensitizer CM34 through donor/receptor regulation strategies, and it is able to achieve long‐retention cell membrane targeting. It is not only an extremely excellent cell membrane targeted tumor theranostic agent, but also found to be a promising potential immune activator. Specifically, CM34 with a larger intramolecular twist angle is more likely to form larger aggregates in aqueous solutions, and the introduction of cyanide group also enhances its interaction with cell membranes, which were key factors hindering molecular penetration of the cell membrane and prolonging its residence time on the cell membrane, providing conditions for further membrane targeted photodynamic therapy. Furthermore, the efflux of contents caused by cell necrosis directly activates the immune response. In summary, this study realizes to clarify and refine all potential mechanisms of action through density functional theory calculations, photophysical property measurements, and cellular level mechanism exploration, providing a new direction for the clinical development of cell membrane targeted anti‐tumor immune activators. [ABSTRACT FROM AUTHOR]

Designing nanomedicines with low toxicity, high targeting, excellent therapeutic effects, and precise release is always the major challenges in clinical cancer treatment. Here, we report a light‐enhanced tandem‐responsive nano delivery platform COF‐B@X‐03 for amplified anti‐tumor efficiency. Biotin‐loaded COF‐B@X‐03 could precisely target tumor cells, and the azo and hydrazone bonds in it would be depolymerized by the overexpressed azoreductase and acidic microenvironment in hypoxic tumors. In vitro experimental results indicate mitochondrial and endoplasmic reticulum stress caused by COF‐B@X‐03 under light is the direct cause of tumor cell death. In vivo experimental data prove COF‐B@X‐03 achieves low oxygen dependent phototherapy, and the maintenance of intratumoral hypoxia provides the possibility for the continuous degradation of COF‐B@X‐03 to generate more reactive oxygen species for tumor photodynamic therapy by released X‐03. In the end, COF‐B@X‐03 phototherapy group achieves higher tumor inhibition rate than X‐03 phototherapy group, which is 81.37 %. Meanwhile, COF‐B@X‐03 significantly eliminates the risk of tumor metastasis. In summary, the construction of this tandem‐responsive nano delivery platform provides a new direction for achieving efficient removal of solid tumors in clinical practice. [ABSTRACT FROM AUTHOR]

Immunogenic cell death (ICD) could activate anti-tumor immune responses, which is highly attractive for improving cancer treatment effectiveness. Here, this work reports a multifunctional arsenic(III) allosteric inhibitor Mech02, which induces excessive accumulation of 1 O 2 through sensitized biocatalytic reactions, leading to cell pyroptosis and amplified ICD effect. After Mech02 is converted to Mech03, it could actualize stronger binding effects on the allosteric pocket of pyruvate kinase M2, further interfering with the anaerobic glycolysis pathway of tumors. The enhanced DNA damage triggered by Mech02 and the pyroptosis of cancer stem cells provide assurance for complete tumor clearance. In vivo experiments prove nanomicelle Mech02-HA NPs is able to activate immune memory effects and raise the persistence of anti-tumor immunity. In summary, this study for the first time to introduce the arsenic(III) pharmacophore as an enhanced ICD effect initiator into nitrogen mustard, providing insights for the development of efficient multimodal tumor therapy agents., (© 2024 Wiley‐VCH GmbH.)