Computed tomography (CT) contrast and radiosensitization usually increase with particle sizes of gold nanoparticles (AuNPs), but there is a huge challenge to improve both by adjusting sizes under the requirements of in vivo application. Here, we report that AuNPs have great size-dependent enhancements on CT imaging as well as radiotherapy (RT) in the size range of 3-50 nm. It is demonstrated that AuNPs with a size of ∼13 nm could simultaneously possess superior CT contrast ability and significant radioactive disruption. The Monte Carlo method is further used to evaluate this phenomenon and indicates that the inhomogeneity of gold atom distributions caused by sizes may influence secondary ionization in whole X-ray interactions. In vivo studies further indicate that this optimally sized AuNP improves real-time CT imaging and radiotherapeutic inhibition of tumors in living mice by effective accumulation at tumors with prolonged in vivo circulation times compared to clinically used small-molecule agents. These results suggest that ∼13 nm AuNPs may serve as multifunctional adjuvants for clinical X-ray theranostic application.

To integrate multiple diagnostic and therapeutic strategies on a single particle through simple and effective methods is still challenging for nanotheranostics. Herein, we develop multifunctional nanotheranostic PB@Au core-satellite nanoparticles (CSNPs) based on Prussian blue nanoparticles (PBNPs) and gold nanoparticles (AuNPs), which are two kinds of intrinsic theranostic nanomaterials, for magnetic resonance (MR)-computed tomography (CT) imaging and synergistic photothermal and radiosensitive therapy (PTT-RT). PBNPs as cores enable T- and T-weighted MR contrast and strong photothermal effect, while AuNPs as satellites offer CT enhancement and radiosensitization. As revealed by both MR and CT imaging, CSNPs realized efficient tumor localization by passively targeted accumulation after intravenous injection. In vivo studies showed that CSNPs resulted in synergistic PTT-RT action to achieve almost entirely suppression of tumor growth without observable recurrence. Moreover, no obvious systemic toxicity of mice confirmed good biocompatibility of CSNPs. These results raise new possibilities for clinical nanotheranostics with multimodal diagnostic and therapeutic coalescent design.

Hypoxia-induced radioresistance is the primary reason for failure of tumor radiotherapy (RT). Changes within the irradiated tumor microenvironment (TME) including oxygen, reactive oxygen species (ROS) and nitric oxide (NO) are closely related to radioresistance. Therefore, there is an urgent need to develop new approaches for overcoming hypoxic radioresistance by incorporating TME regulation into current radiotherapeutic strategies.Methods: Herein, we explored a radiation-responsive nanotheranostic system to enhance RT effects on hypoxic tumors by multi-way therapeutic effects. This system was developed by loading S-nitrosothiol groups (SNO, a NO donor) and indocyanine green (ICG, a photosensitizer) onto mesoporous silica shells of Eu3+-doped NaGdF4 scintillating nanocrystals (NSC).Results: Under X-ray radiation, this system can increase the local dosage by high-Z elements, promote ROS generation by X-ray-induced photodynamic therapy, and produce high levels of NO to enhance tumor-killing effects and improve hypoxia via NO-induced vasodilation. In vitro and in vivo studies revealed that this combined strategy can greatly reinforce DNA damage and apoptosis of hypoxic tumor cells, while significantly suppressing tumor growth, improving tumor hypoxia and promoting p53 up-regulation and HIF1α down-regulation. In addition, this system showed pronounced tumor contrast performance in T1-weighted magnetic resonance imaging and computed tomography.Conclusion: This work demonstrates the great potential of scintillating nanotheranostics for multimodal imaging-guided X-ray radiation-triggered tumor combined therapy to overcome radioresistance.

Screening and assessing diabetic retinopathy (DR) are essential for reducing morbidity associated with diabetes. Macular ischemia is known to correlate with the severity of retinopathy. Recent studies have shown that optical coherence tomography angiography (OCTA), with intrinsic contrast from blood flow motion, is well suited for quantified analysis of the avascular area, which is potentially a useful biomarker in DR. In this study, we propose the first deep learning solution to segment the avascular area in OCTA of DR. The network design consists of a multi-scaled encoder-decoder neural network (MEDnet) to detect the non-perfusion area in 6 × 6 mm 2 and in ultra-wide field retinal angiograms. Avascular areas were effectively detected in DR subjects of various disease stages as well as in the foveal avascular zone of healthy subjects.

BackgroundThe main objective of this study was to evaluate the efficacy of integrating the blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) and diffusion tensor imaging (DTI) data into radiation treatment planning for high-grade gliomas located near the primary motor cortexes (PMCs) and corticospinal tracts (CSTs).MethodsA total of 20 patients with high-grade gliomas adjacent to PMCs and CSTs between 2012 and 2014 were recruited. The bilateral PMCs and CSTs were located in the normal regions without any overlapping with target volume of the lesions. BOLD-fMRI, DTI and conventional MRI were performed on patients (Karnofsky performance score ≥ 70) before radical radiotherapy treatment. Four different imaging studies were conducted in each patient: a planning computed tomography (CT), an anatomical MRI, a DTI and a BOLD-fMRI. For each case, three treatment plans (3DCRT, IMRT and IMRT_PMC&CST) were developed by 3 different physicists using the Pinnacle planning system.ResultsOur study has shown that there was no significant difference between the 3DCRT and IMRT plans in terms of dose homogeneity, but IMRT displayed better planning target volume (PTV) dose conformity. In addition, we have found that the Dmax and Dmean to the ipsilateral and contralateral PMC and CST regions were considerably decreased in IMRT_PMC&CST group (p < 0.001).ConclusionsIn conclusion, integration of BOLD-fMRI and DTI into radiation treatment planning is feasible and beneficial. With the assistance of the above-described techniques, the bilateral PMCs and CSTs adjacent to the target volume could be clearly marked as OARs and spared during treatment.