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Tumor hypoxia diminishes the effectiveness of traditional type II photodynamic therapy (PDT) due to oxygen consumption. Type I PDT, which can operate independently of oxygen, is a viable option for treating hypoxic tumors. In this study, we have designed and synthesized JSK@PEG-IR820 NPs that are responsive to the tumor microenvironment (TME) to enhance type I PDT through glutathione (GSH) depletion. Our approach aims to expand the sources of therapeutic benefits by promoting the generation of superoxide radicals (O2−.) while minimizing their consumption. The diisopropyl group within PEG-IR820 serves a dual purpose: it functions as a pH sensor for the disassembly of the NPs to release JSK and enhances intermolecular electron transfer to IR820, facilitating efficient O2−. generation. Simultaneously, the release of JSK leads to GSH depletion, resulting in the generation of nitric oxide (NO). This, in turn, contributes to the formation of highly cytotoxic peroxynitrite (ONOO−.), thereby enhancing the therapeutic efficacy of these NPs. NIR-II fluorescence imaging guided therapy has achieved successful tumor eradication with the assistance of laser therapy.

The management of diabetic wounds poses significant challenges due to persistent bacterial infections and chronic inflammation caused by hyperglycemia. Herein, a sequential two‐phase treatment strategy involving a reactive oxygen species (ROS) burst in the first phase for anti‐infection is proposed, followed by a benign level of ROS in the second phase for wound regeneration. To this end, ultra‐small manganese oxide nanodots (BM‐NDs) are incorporated into a gelatin methacrylamide (GelMA) hydrogel via a ROS‐responsive linker to form GelMA@BM dressing. The BM‐NDs catalyze a self‐cascade reaction that decomposes glucose into hydrogen peroxide, generates hydroxyl radicals (·OH), and simultaneously depletes glutathione. Upon application on diabetic wounds, BM‐NDs are rapidly released from the hydrogel due to endogenous ROS exposure, leading to high levels of ·OH that effectively eliminate bacteria and promote macrophage polarization to M1 phenotype, thereby facilitating phagocytosis of bacteria. With the consumption of glucose and degradation of BM‐NDs, ROS in the wound area declines to a benign level, which stimulates polarization of M2 macrophages and promotes wound healing. This two‐phase treatment strategy based on GelMA@BM dressing demonstrates potent antibacterial and pro‐healing efficacy, showcasing its potential for clinical translation.

177Lu is a radioisotope that has become increasingly popular as a therapeutic agent for treating various conditions, including neuroendocrine tumors and metastatic prostate cancer. 177Lu-tagged radioligands are molecules precisely designed to target and bind to specific receptors or proteins characteristic of targeted cancer. This review paper will present an overview of the available 177Lu-labelled radioligands currently used to treat patients. Based on recurring, active, and completed clinical trials and other available literature, we evaluate current status, interests, and developments in assessing patient-specific dosimetry, which will define the future of this particular treatment modality. In addition, we will discuss the challenges and opportunities of the existing dosimetry standards to measure and calculate the radiation dose delivered to patients, which is essential for ensuring treatments' safety and efficacy. Finally, this article intends to provide an overview of the current state of 177Lu-tagged radioligand therapy and highlight the areas where further research can improve patient treatment outcomes. [ABSTRACT FROM AUTHOR]