Nanoenzymes perceive the properties of enzyme‐like catalytic activity, thereby offering significant cancer therapy potential. In this study, Fe3O4@MnO2, a magnetic field (MF) targeting nanoenzyme with a core‐shell structure, is synthesized and applied to radiation enhancement with using glucose oxidase (GOX) for combination therapy. The glucose is oxidized by the GOX to produce excess H2O2 in an acidic extracellular microenvironment, following which the MnO2 shell reacts with H2O2 to generate O2 and overcome hypoxia. Concurrently, intracellular glutathione (GSH)—which limits the effects of radiotherapy (RT)—can be oxidized by the MnO2 shell while the latter is reduced to Mn2+ for T1‐weighed MRI. The core Fe3O4, with its good magnetic targeting ability, can be utilized for T2‐weighed MRI. In summary, the work demonstrates that Fe3O4@MnO2, as a dual T1‐ and T2‐weighed MRI contrast agent with strong biocompatibility, exhibits striking potential for radiation enhancement under magnetic targeting.
BackgroundTo report our experience in planning and delivering total marrow irradiation (TMI) and total marrow and lymphatic irradiation (TMLI) in patients with hematologic malignancies.MethodsTwenty-seven patients undergoing bone marrow transplantation were treated with TMI/TMLI using Helical Tomotherapy (HT). All skeletal bones exclusion of the mandible comprised the treatment target volume and, for TMLI, lymph node chains, liver, spleen and/or brain were also included according to the clinical indication. Planned dose of 8Gy in 2 fractions was delivered over 1 day for TMI while 10Gy in 2 fractions BID was used for TMLI. Organs at risk (OAR) contoured included the brain, brainstem, lens, eyes, optic nerves, parotids, oral cavity, lungs, heart, liver, kidneys, stomach, small bowel, bladder and rectum. In particular, a simple method to avoid hot or cold doses in the overlapping region was implemented and the plan sum was adopted to evaluate dose inhomogeneity. Furthermore, setup errors from 54 treatments were summarized to gauge the effectiveness of immobilization.ResultsDuring the TMI/TMLI treatment, no acute adverse effects occurred during the radiation treatment. Two patients suffered nausea or vomiting right after radiation course. For the 9 patients treated with TMI, the median dose reduction of major organs varied 30–65% of the prescribed dose, substantially lower than the traditional total body irradiation (TBI). Meanwhile, average biological equivalent doses to OARs with 8Gy/2F TMI approach were not different from the conventional 12Gy/6F TMI approach. In the dose junction region, the 93% of PTV was covered by the prescribed dose without obvious hotspots. For the 27 patients, the overall setup corrections were lower than 3 mm except those in the SI direction for abdomen-pelvis region, demonstrating excellent immobilization.ConclusionThe present study confirmed the technical feasibility of HT-based TMI/TMLI delivering 8-10Gy in 2 fractions over 1 day. For patients undergoing hematopoietic cell transplantation the proposed 8Gy/2F TMI (or 10Gy/2F TMLI) strategy may be a novel approach to improve delivery efficiency, increase effective radiation dose to target while maintaining low risk of severe organ toxicities.
Rational: Interstitial brachytherapy (BT) is a promising radiation therapy for cancer; however, the efficacy of BT is limited by tumor radioresistance. Recent advances in materials science and nanotechnology have offered many new opportunities for BT. Methods: In this work, we developed a biomimetic nanotheranostic platform for enhanced BT. Core-shell Au@AuPd nanospheres (CANS) were synthesized and then encapsulated in platelet (PLT)-derived plasma membranes. Results: The resulting PLT/CANS nanoparticles efficiently evaded immune clearance and specifically accumulated in tumor tissues due to the targeting capabilities of the PLT membrane coating. Under endoscopic guidance, a BT needle was manipulated to deliver appropriate radiation doses to orthotopic colon tumors while sparing surrounding organs. Accumulated PLT/CANS enhanced the irradiation dose deposition in tumor tissue while alleviating tumor hypoxia by catalyzing endogenous H 2 O 2 to produce O 2 . After treatment with PLT/CANS and BT, 100% of mice survived for 30 days. Conclusions: Our work presents a safe, robust, and efficient strategy for enhancing BT outcomes when adapted to treatment of intracavitary and unresectable tumors.
This case series evaluated the delivery of radiotherapy in 209 patients with cancer during the COVID-19 outbreak in Wuhan, China.
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