Radiotherapy combined with nano-biomaterials for cancer radio-immunotherapy.

Radiotherapy (RT) plays an important role in tumor therapy due to its noninvasiveness and wide adaptation. In recent years, radiation therapy has been discovered to induce an anti-tumor immune response, which arouses widespread concern among scientists and clinicians. In this review, we highlight recent advances in the applications of nano-biomaterials for radiotherapy-activated immunotherapy. We first discuss the combination of different radiosensitizing nano-biomaterials and immune checkpoint inhibitors to enhance tumor immune response and improve radiotherapy efficacy. Subsequently, various nano-biomaterials-enabled tumor oxygenation strategies are introduced to alleviate the hypoxic tumor environment and amplify the immunomodulatory effect. With the aid of nano-vaccines and adjuvants, radiotherapy refreshes the host's immune system. Additionally, ionizing radiation responsive nano-biomaterials raise innate immunity-mediated anti-tumor immunity. At last, we summarize the rapid development of immune modulatable nano-biomaterials and discuss the key challenge in the development of nano-biomaterials for tumor radio-immunotherapy. Understanding the nano-biomaterials-assisted radio-immunotherapy will maximize the benefits of clinical radiotherapy and immunotherapy and facilitate the development of new combinational therapy modality.

In Situ Formed Z-Scheme Graphdiyne Heterojunction Realizes NIR-Photocatalytic Oxygen Evolution and Selective Radiosensitization for Hypoxic Tumors.

Photon radiotherapy is a common tool in the armory against tumors, but it is limited by hypoxia-related radioresistance of tumors and radiotoxicity to normal tissues. Here, we constructed a spatiotemporally controlled synergistic therapy platform based on the heterostructured CuO@Graphdiyne (CuO@GDY) nanocatalyst for simultaneously addressing the two key problems above in radiotherapy. First, the in situ formed Z-scheme CuO@GDY heterojunction performs highly efficient and controlled photocatalytic O2 evolution upon near-infrared (NIR) laser stimulation for tumor hypoxia alleviation. Subsequently, the CuO@GDY nanocatalyst with X-ray-stimulated Cu+ active sites can accelerate Fenton-like catalysis of ·OH production by responding to endogenous H2O2 for the selective killing of tumor cells rather than normal cells. In this way, the sequential combination of NIR-triggered photocatalytic O2 production and X-ray-accelerated Fenton-like reaction can lead to a comprehensive radiosensitization. Overall, this synergism underscores a controllable and precise therapy modality for simultaneously unlocking the hypoxia and non-selectivity in radiotherapy.

Primary hypertension in a postoperative paraganglioma patient: A case report.

BACKGROUND: Primary hypertension is a common clinical disease. Pheochromocytoma and paraganglioma is a rare cause of secondary hypertension. The diagnosis of the latter is still difficult, and the relationship between the two is not clear. The successful diagnosis of this case confirmed that standardized etiological investigation of secondary hypertension is necessary, contributes to the accurate diagnosis of rare diseases, and is conducive to the formulation or optimization of treatment plans. It shows an example of the coexistence of primary hypertension and secondary hypertension. CASE SUMMARY: The patient was a 54-year-old male and was hospitalized with high blood pressure for 4 years. The patient's blood pressure was measured at 150/100 mmHg during physical examination 4 years ago and had no paroxysmal or persistent elevated blood pressure, no typical triad of headache, palpitation, and sweating, without postural hypotension. After taking nifedipine sustained release tablets intermittently, the blood pressure did not meet the standard. Physical examination revealed blood pressure of 180/120 mmHg. There was no abnormality in cardiopulmonary and abdominal examination. The results of blood and/or urinary catecholamines/metanephrine and normetanephrine before and after operation were normal. Fundus examination revealed retinal arteriosclerosis in both eyes. There was a history of paraganglioma diagnosed by pathology after retroperitoneal tumor resection, a family history of hypertension, and a history of passive smoking. The clinical diagnosis was subclinical paraganglioma, primary hypertension, and hypertensive fundus lesions. The patient's blood pressure was regulated, blood lipid was reduced, and anti-inflammatory, and symptomatic support were given. After treatment, the blood pressure was stable and up to standard without discomfort symptoms. CONCLUSION: Subclinical paraganglioma and primary hypertension can coexist. The holistic thinking in clinical practice is helpful to the early diagnosis of rare diseases.

Novel Copper(II) Complex with a 4-Acylpyrazolone Derivative and Coligand Induce Apoptosis in Liver Cancer Cells.

A novel pyrazolone-based copper complex [CuL(phen)(CH3OH)][CuL(phen)]·CH3CH2OH·CH3OH (P-FAH-Cu-phen) was synthesized and characterized. The asymmetric structural unit of P-FAH-Cu-phen was composed of two independent complex units [CuL(phen)(CH3OH)] and [CuL(phen)]:Cu12+ center with six coordination mode and Cu22+ center with five coordination mode. The growth of BEL-7404 cells and H22 cells was significantly inhibited by P-FAH-Cu-phen with IC50 values of 1.175 µg/mL and 1.097 µg/mL, respectively, which were much lower than IC50 of cisplatin for BEL-7404 cells (23.32 µg/mL) and H22 cells (27.5 µg/mL). P-FAH-Cu-phen induced cell cycle arrest at G2/M and apoptosis in BEL-7404 cells through mitochondria- and endoplasmic reticulum stress-associated pathways. Moreover, P-FAH-Cu-phen significantly suppressed the migration of BEL-7404 cells and the tumor growth in H22 tumor mouse model without severe side effects and improved the survival of tumor mice. The results suggested that P-FAH-Cu-phen might be a potential drug candidate for the treatment of live cancer.

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials.

Carbon monoxide (CO) therapy has emerged as a hot topic under exploration in the field of gas therapy as it shows the promise of treating various diseases. Due to the gaseous property and the high affinity for human hemoglobin, the main challenges of administrating medicinal CO are the lack of target selectivity as well as the toxic profile at relatively high concentrations. Although abundant CO releasing molecules (CORMs) with the capacity to deliver CO in biological systems have been developed, several disadvantages related to CORMs, including random diffusion, poor solubility, potential toxicity, and lack of on-demand CO release in deep tissue, still confine their practical use. Recently, the advent of versatile nanomedicine has provided a promising chance for improving the properties of naked CORMs and simultaneously realizing the therapeutic applications of CO. This review presents a brief summarization of the emerging delivery strategies of CO based on nanomaterials for therapeutic application. First, an introduction covering the therapeutic roles of CO and several frequently used CORMs is provided. Then, recent advancements in the synthesis and application of versatile CO releasing nanomaterials are elaborated. Finally, the current challenges and future directions of these important delivery strategies are proposed.