Hypoxia not only promotes tumor metastasis but also strengthens tumor resistance to therapies that demand the involvement of oxygen, such as radiation therapy and photodynamic therapy (PDT). Herein, taking advantage of the high reactivity of manganese dioxide (MnO2) nanoparticles toward endogenous hydrogen peroxide (H2O2) within the tumor microenvironment to generate O2, multifunctional chlorine e6 (Ce6) loaded MnO2 nanoparticles with surface polyethylene glycol (PEG) modification (Ce6@MnO2‐PEG) are formulated to achieve enhanced tumor‐specific PDT. In vitro studies under an oxygen‐deficient atmosphere uncover that Ce6@MnO2‐PEG nanoparticles could effectively enhance the efficacy of light‐induced PDT due to the increased intracellular O2 level benefited from the reaction between MnO2 and H2O2, the latter of which is produced by cancer cells under the hypoxic condition. Owing to the efficient tumor homing of Ce6@MnO2‐PEG nanoparticles upon intravenous injection as revealed by T1‐weighted magnetic resonance imaging, the intratumoral hypoxia is alleviated to a great extent. Thus, in vivo PDT with Ce6@MnO2‐PEG nanoparticles even at a largely reduced dose offers remarkably improved therapeutic efficacy in inhibiting tumor growth compared to free Ce6. The results highlight the promise of modulating unfavorable tumor microenvironment with nanotechnology to overcome current limitations of cancer therapies.

Exogenous FeIII can be used for cancer magnetic resonance (MR) imaging and potentially for cancer treatment by a ferroptosis pathway or photothermal ablation. To achieve this, effective and accurate delivery of FeIII to cancerous sites is critical, requiring a balance of release kinetics of Fe3+ in tumorous and normal tissues. A nanoprobe is described consisting of upconversion luminescence (UCL) nanoparticles as a core and a coordinatively unsaturated FeIII‐containing Fe3+/gallic acid complex as a shell. Owing to the introduction of an unsaturated coordination structure, FeIII in the nanoprobe can be released only in the tumor microenvironment in response to the lightly acidic pH. The multiple UCLs are used for quantitatively visualizing the release of Fe3+ in vivo, whilst the release resultant serves as a photothermal agent. This nanoprobe exhibited ligand‐free tumor targeting ability, activatable MR imaging performance, and efficacious therapeutic effects against tumors in vivo.

Abstract. An elevated rate of glucose consumption and the dependency on aerobic glycolysis for ATP generation have long been observed in cancer cells, a phenomenon known as the Warburg effect. The altered energy metabolism in cancer cells provides an attractive opportunity for developing novel cancer therapeutic strategies. Lactate dehydrogenase (LDH), which catalyzes the transformation of pyruvate to lactate, plays a vital role in the process of glycolysis. It has been reported that the level of LDH-A expression is increased both in head and neck cancer cells and in the blood serum of nasopharyngeal carcinoma (NPC) patients, and is associated with poor prognosis. However, the effect of LDH-A inhibition on NPC cells remains unknown. Here, in the present study, we found that oxamate, a classical inhibitor of LDH-A, suppressed cell proliferation in a dose-and time-dependent manner both in CNE-1 and CNE-2 cells, two NPC cancer cell lines. LDH inhibition by oxamate induced G 2 /M cell cycle arrest via downregulation of the CDK1/cyclin B1 pathway and promoted apoptosis through enhancement of mitochondrial ROS generation. N-acetylcysteine, a specific scavenger of ROS, significantly blocked the growth inhibition effect induced by oxamate. We also identified that oxamate increased sensitivity to ionizing radiation in the two NPC cancer cell lines. Furthermore, we verified similar results in tumor xenograft models. Collectively, these results suggest that LDH-A may serve as a promising therapeutic target for NPC treatment.

131 I whole-body scintigraphy (WBS) is a highly sensitive method for the detection of differentiated thyroid tumors and metastases. However, a lack of anatomic landmarks and the physiologic accumulation of the tracer complicate interpretation of the images. This prospective study was designed to evaluate the incremental value of 131 I SPECT/CT over planar WBS in the management of patients with differentiated thyroid carcinoma (DTC). Methods: Planar imaging was performed on 66 consecutive DTC patients who were considered to have locally advanced or metastatic disease after total or nearly total thyroidectomy. SPECT/CT was added for patients whose planar findings were inconclusive. The planar images were interpreted by 2 experienced nuclear medicine physicians. Interpretation of the SPECT/CT images was a consensus opinion of one of the nuclear medicine physicians and an experienced radiologist. Fusion images were considered to improve image interpretation when they better localized sites of increased 131 I uptake. The final diagnosis was verified by pathologic findings, other imaging modalities, and clinical follow-up. Both site-based and patient-based analyses were performed, and the impact of SPECT/CT results on therapeutic strategy was assessed. Results: A total of 232 foci were observed by 131 I WBS, including 33.2% of foci localized in the thyroid bed, 62.1% due to malignant lesions, and 4.7% caused by nonthyroidal physiologic or benign uptake or a contaminant. Overall, 37 SPECT/CT studies were performed on 23 patients, whose planar images showed 81 inconclusive lesions. Precise localization and characterization of 131 I-avid foci were achieved through 131 I SPECT/CT in 69 (85.2%) and 67 (82.7%) of the 81 foci, respectively. Fusion images were considered to be of benefit in 17 (73.9%) of 23 patients. The therapeutic strategy was changed in 8 (47.1%) of 17 patients. Uncommon metastatic lesions were found in 9 (13.6%) of 66 patients with regard to SPECT/CT fusion images. Conclusion: Fusion of SPECT and CT images was of incremental value over WBS in increasing diagnostic accuracy, reducing pitfalls, and modifying therapeutic strategies in 73.9% of DTC patients. As SPECT/CT techniques emerge, 131 I SPECT/CT may demonstrate higher value than WBS in the management of DTC.

An inactivated vaccine for severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) was evaluated in rhesus monkeys. The monkeys were inoculated intramuscularly (i.m.) with 0.5, 5, 50, or 5000 microg of vaccine, or PBS as control, and boosted on day 7. After 3 weeks, they were challenged with the NS-1 strain of SARS-CoV. The humoral and mucosal immune responses, clinical signs, chemical indices and viremia were monitored following the immunization and challenge. The control animals who received PBS developed atypical SAR-CoV infection after viral challenge, according to clinical, virological and pathological findings. No systematic side effects were observed in vaccinated animals post-immunization, even in at the high dose of 5000 microg. The 50 microg dosage of vaccine elicited SARS-CoV specific immune responses against viral infection as compared to the partial immunity elicited by 0.5 and 5 microg doses. The results show that this inactivated vaccine can induce effective concomitant humoral and mucosal immunity against SARS-CoV infection, is safe in monkeys, and the vaccine maybe a good candidate for clinical trials.

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Inorganic nanoparticles as a versatile nanoplatform have been broadly applied in the diagnosis and treatment of cancers due to their inherent superior physicochemical properties (including magnetic, thermal, optical, and catalytic performance) and excellent functions (e.g., imaging, targeted delivery, and controlled release of drugs) through surface functional modification or ingredient dopant. However, in practical biological applications, inorganic nanomaterials are relatively difficult to degrade and excrete, which induces a long residence time in living organisms and thus may cause adverse effects, such as inflammation and tissue cysts. Therefore, the development of biodegradable inorganic nanomaterials is of great significance for their biomedical application. This Review will focus on the recent advances of degradable inorganic nanoparticles for cancer theranostics with highlight on the degradation mechanism, aiming to offer an in-depth understanding of degradation behavior and related biomedical applications. Finally, key challenges and guidelines will be discussed to explore biodegradable inorganic nanomaterials with minimized toxicity issues, facilitating their potential clinical translation in cancer diagnosis and treatment.

Sorafenib at a dose of 200 mg twice daily has a potential therapeutic effect and is well tolerated in Chinese patients with PTC and radioiodine-refractory pulmonary metastases. Further study is warranted with a larger cohort of patients.