The Use of Bionic Prodrugs for the Enhancement of Low Dose Radiotherapy

Radiotherapy (RT) is a standard treatment strategy for many cancer types, but the need to frequently apply high doses of ionizing radiation in order to achieve therapeutic efficacy can cause severe harm to healthy tissues, leading to adverse patient outcomes. In an effort to minimize these toxic side effects, we herein sought to design a novel approach to the low-dose RT treatment of hypoxic tumors using a Tirapazamine (TPZ)-loaded exosome (EXO) nanoplatform (MT). This MT platform was synthesized via loading EXOs with TPZ, which is a prodrug that is activated when exposed to hypoxic conditions. MT application was able to achieve effective tumor inhibition at a relatively low RT dose (2 Gy) that was superior to standard high-dose (6 Gy) RT treatment with specific targeting to the hypoxic region of tumor. RT-mediated oxygen consumption further aggravated hypoxic conditions to improve TPZ activation and treatment efficacy. Together, our findings demonstrate the clinical promise of this MT platform as a novel tool for the efficient radiosensitization and treatment of cancer patients.

Oxygen sensing ability of positronium atom for tumor hypoxia imaging

Positronium (Ps), a hydrogen-like atom consisting of a positron and an electron, is efficiently formed in the human body during positron emission tomography (PET) examination, and its decay rate into gamma-ray photons is significantly influenced by the chemical environment, especially the dissolved oxygen concentration (pO2) due to the unpaired electrons. However, the functionality of PET has been underestimated by neglecting the specific information provided by Ps. By comparing the decay rates in O2-, N2-, and air-saturated waters, here we show that Ps probes the absolute value of pO2 with a good linearity and a resolution better than 10 mmHg. This is a sufficient sensitivity for discriminating a hypoxic region in a tumor at approximately 6 mmHg from healthy tissues at approximately 40 mmHg. This method depends only on the fundamental properties of Ps and is independent of specific radiopharmaceuticals. The applications of Ps spin states and reactions will greatly enhance PET functionalities in the next decade.

A numerical model study of the main factors contributing to hypoxia and its sub-seasonal to interannual variability off the Changjiang Estuary

A three-dimensional physical-biological model of marginal seas of China was used to analyze variations in hypoxic conditions and identify the main processes controlling their generation off the Changjiang Estuary. The model was validated against available observations and reproduces the observed temporal and spatial variability of hypoxia. Dissolved oxygen concentrations undergo a seasonal cycle, with minima generally occurring in August or September, and vary latitudinally with a longer duration of low-oxygen concentrations in the southern part of the hypoxic region. Interannual variations of hypoxic extent are primarily associated with variations in river discharge and wind forcing, with high river discharge promoting hypoxia generation. At synoptic time scales, strong wind events (e.g. typhoons) can disrupt hypoxic conditions. During the oxygen-depleted period (March–August), air–sea exchange acts as an oxygen sink in oversaturated surface waters. In the subsurface, biological oxygen consumption tends to dominate, but lateral physical transport of oxygen can be comparable during hypoxic conditions. Oxygen consumption in the water column exceeds that of the sediment when integrated over the whole water column, but sediment consumption is dominant below the pycnocline. Vertical diffusion of oxygen acts as the primary oxygen source below the pycnocline and shows a seasonal cycle similar to that of primary production. Advection of oxygen in the bottom waters acts as an oxygen sink in spring but becomes a source during hypoxic conditions in summer especially in the southern part of the hypoxic region, which is influenced by open-ocean intrusions.

GLYCOLYTIC 2-DEOXY-D-GLUCOSE PERIOCULAR INHIBITOR SEBAGAI TERAPI ADJUVANT PADA RETINOBLASTOMA

Retinoblastoma is the most common intraocular tumor in children. Retinoblastoma tumors consist of areas with high angiogenic activity and other areas with low oxygen pressure conditions. Tumor cells that survive in this hypoxic region have been shown to be resistant to chemotherapy and radiation, namely standard retinoblastoma therapy which selectively targets rapidly dividing cell populations, so that therapy is needed that can reach up to the hypoxic cells. 2-deoxy-D-glucose (2-DG) has been shown to be effective in reducing hypoxic areas in tumors, reducing tumor buds, and inhibiting angiogenesis. to discuss the glycolytic 2-DG inhibitors as adjuvant therapy in retinoblastoma. The authors searched for medical articles in the PubMed and ResearchGate literature databases with the keywords treatment, 2-deoxy-D-glucose, 2-DG, retinoblastoma, and cancer. The words are combined with OR or AND using Boolean logic. Based on the selection according to the inclusion and exclusion criteria, 4 articles were used as the main reference for writing this review literature. 2-DG will disregulate (inhibit) the process of angiogenesis through upregulation of Estrogen Receptor 1 Nuclear (ESR 1), ubiquitin, jun activation domain binding protein 1 (JAB1), G-protein alpha S, and CAPER in the apical part of the tumor and B3GNT1 upregulation , CEPT1, PABPC1, myotrophin, HAX1 in the postero-lateral part of the tumor. H3, DTX1, RPL12, and bone morphogenic (BMP) histones are also upregulated so that hypoxia can be inhibited. With this mechanism, the tumor burden can be suppressed. Glycolytic 2-DG inhibitors with anti-angiogenesis and anti-hypoxic abilities can be developed as adjuvant therapy for advanced retinoblastoma patients.