Multimodality imaging based on multifunctional nanocomposites holds great promise to fundamentally augment the capability of biomedical imaging. Specifically, photoacoustic and fluorescence dual-modality imaging is gaining much interest because of their non-invasiveness and the complementary nature of the two modalities in terms of imaging resolution, depth, sensitivity, and speed. Herein, using a green and facile method, we synthesize indocyanine green (ICG) loaded, polyethylene glycol (PEG)ylated, reduced nano-graphene oxide nanocomposite (rNGO-PEG/ICG) as a new type of fluorescence and photoacoustic dual-modality imaging contrast. The nanocomposite is shown to have minimal toxicity and excellent photoacoustic/fluorescence signals both in vitro and in vivo. Compared with free ICG, the nanocomposite is demonstrated to possess greater stability, longer blood circulation time, and superior passive tumor targeting capability. In vivo study shows that the circulation time of rNGO-PEG/ICG in the mouse body can sustain up to 6 h upon intravenous injection; while after 1 day, no obvious accumulation of rNGO-PEG/ICG is found in any major organs except the tumor regions. The demonstrated high fluorescence/photoacoustic dual contrasts, together with its low toxicity and excellent circulation life time, suggest that the synthesized rNGO-PEG/ICG can be a promising candidate for further translational studies on both the early diagnosis and image-guided therapy/surgery of cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-016-1288-x) contains supplementary material, which is available to authorized users.

Photodynamic therapy (PDT) holds promise for focal therapy of prostate cancer (PCa). However, the therapeutic efficacy needs improvement, and further development of PDT for PCa has challenges, including uncertainty of photosensitizers (PSs) accumulation at the tumor site and difficulty in visualizing lesions using conventional ultrasound (US) imaging. We have developed novel porphyrin-grafted lipid (PGL) microbubbles (MBs; PGL-MBs) and propose a strategy to integrate PGL-MBs with US imaging to address these limitations and enhance PDT efficacy.Methods: PGL-MBs have two functions: imaging guidance by contrast-enhanced ultrasound (CEUS) and targeted delivery of PSs by ultrasound targeted microbubble destruction (UTMD). PGL-MBs were prepared and characterized before and after low-frequency US (LFUS) exposure. Then, in vitro studies validated the efficacy of PDT with PGL-MBs in human prostate cancer PC3 cells. PC3-xenografted nude mice were used to validate CEUS imaging, accumulation at the tumor site, and in vivo PDT efficacy.Results: PGL-MBs showed good contrast enhancement for US imaging and were converted into nanoparticles upon LFUS exposure. The resulting uniquely structured nanoparticles avoided porphyrin fluorescence quenching and efficiently accumulated at the tumor site through the sonoporation effect created with the assistance of US to achieve excellent PDT efficacy.Conclusions: This is the first preclinical investigation of MBs applied in PDT for PCa. PGL-MBs possess favorable CEUS imaging effects to enhance the localization of tumors. PGL-MBs with LFUS control PS accumulation at the tumor site to achieve highly effective PDT of PCa. This strategy carries enormous clinical potential for PCa management.

The aim of the present study was to quantitatively diagnose and monitor the therapy response of hepatic ischemia-reperfusion injury (IRI) with the use of targeted ultrasound (US) imaging. Targeted microbubbles (MBs) were fabricated, and the binding of intracellular adhesion molecule 1 (ICAM-1) antibodies to MBs was observed. To establish a quantitative method based on targeted US imaging, contrast-enhanced US was applied for IRI rats. After andrographolide treatment, the IRI rats were subjected to the quantitative targeted US imaging for a therapeutic effect. Effective binding of ICAM-1 antibodies to MBs was observed. According to the quantitative targeted US imaging, the ICAM-1 normalized intensity difference (NID) in the IRI rats (38.74 ± 15.08%) was significantly higher than that in the control rats (10.08 ± 2.52%, p = 0.048). Further, different degrees of IRI (mild IRI, moderate to severe IRI) were distinguished by the use of the NID (37.14 ± 2.14%, 22.34 ± 1.08%, p = 0.002). Analysis of mRNA expression demonstrated the accuracy of analyzing the NID by using quantitative targeted US imaging (R = 0.7434, p < 0.001). Andrographolide treatment resulted in an obviously weakened NID of ICAM-1 (17.7 ± 4.8% vs 34.2 ± 6.6%, p < 0.001). The study showed the potential of the quantitative targeted US imaging method for the diagnosis and therapeutic monitoring of IRI.

AimTo explore whether ablation safety could be improved by ultrasound (US)-magnetic resonance (MR) fusion imaging for hepatocellular carcinoma (HCC) proximal to the hilar bile ducts (HBDs) through a preliminary comparative study.MethodsBetween January 2014 and June 2019, 18 HCC nodules proximal to the HBDs were included in a US-MR fusion imaging-assisted radiofrequency ablation (RFA) group (study group), while 13 HCC nodules in a similar location were included as a control group. For the study group, the tumor and adjacent bile ducts were outlined on preprocedural MR images. Procedural ablation planning was conducted to assess the feasibility of ablating the tumors while avoiding biliary injury. Such tumors were then ablated under US-MR fusion imaging guidance. The control group nodules were ablated under conventional ultrasound guidance. Baseline characteristics and outcomes were compared between the groups.ResultsAfter preprocedural assessment, 14 of 18 patients with tumors that were feasible to ablate underwent US-MR fusion imaging-assisted RFA. No biliary complications were observed in these 14 patients; the complication rate was significantly lower in the study group than in the control group (30.8%, 4/13) (P = 0.041). There was no significant difference in the technique efficacy rates [92.9% (13/14) versus 100% (13/13), P = 1] or local progression rates [7.1% (1/14) versus 7.7% (1/13), P = 1] between the study and control groups.ConclusionsUS-MR fusion imaging may be a non-invasive means for assisting RFA of HCC nodules proximal to the HBDs and ensuring ablation safety.

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