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Early identification and treatment of hepatocellular carcinoma is very important for improving the prognosis and survival rate of the patient. To enhance the visualization and treatment efficiency of HCC, a theranostic agent has been developed that combines photoacoustic/fluorescence imaging with photothermal therapy for cancer. We report the synthesis of multifunctional theranostic SP94-modified polypyrrole (PPy)-BSA-ICG nanoparticles by a simple method. The multifunctional theranostic agent helped to combine two modes of imaging modalities, i.e. photoacoustic and near infrared (NIR) fluorescence imaging, together with photothermal therapy. These nanoparticles exhibited an excellent stability in physiological solutions (PBS, pH 7.4 at 37 °C), a higher tumor accumulation as compared to the unmodified nanoparticles, and minimal nonspecific uptake by other normal organs such as liver and spleen. Most importantly, the nanoparticles could effectively kill the tumor through photothermal therapy with no tumor recurrence upon a single laser irradiation event. These results indicate that SP94-modified PPy-BSA-ICG is potentially a promising theranostic agent for image-guided cancer therapy as it overcomes the limitations of each of the imaging modalities and thus improves the therapeutic efficiency and reduces the side effects.

Tumor cell complete extinction is a crucial measure to evaluate antitumor efficacy. The difficulties in defining tumor margins and finding satellite metastases are the reason for tumor recurrence. A synergistic method based on multimodality molecular imaging needs to be developed so as to achieve the complete extinction of the tumor cells. In this study, graphene oxide conjugated with gold nanostars and chelated with Gd through 1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid (DOTA) (GO-AuNS-DOTA-Gd) were prepared to target HCC-LM3-fLuc cells and used for therapy. For subcutaneous tumor, multimodality molecular imaging including photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) and the related processing techniques were used to monitor the pharmacokinetics process of GO-AuNS-DOTA-Gd in order to determine the optimal time for treatment. For orthotopic tumor, MRI was used to delineate the tumor location and margin in vivo before treatment. Then handheld photoacoustic imaging system was used to determine the tumor location during the surgery and guided the photothermal therapy. The experiment result based on orthotopic tumor demonstrated that this synergistic method could effectively reduce tumor residual and satellite metastases by 85.71% compared with the routine photothermal method without handheld PAI guidance. These results indicate that this multimodality molecular imaging-guided photothermal therapy method is promising with a good prospect in clinical application.

Early detection and therapy of esophageal cancer is very important for improving the prognosis and survival rate of the patient. A theranostic agent that combines multimodal imaging with cancer therapy may be used for augmenting the visualization and treatment of the cancer. Herein, we report the synthesis of a hollow tantalum oxide (TaO x ) nanoparticle that was successfully engineered by encapsulation of polypyrrole (PPy) and doxorubicin (DOX) in the core and conjugation with a near infrared fluorescence dye (NIRDye800) on the shell of the hollow TaO x nanoparticles. The as-prepared core/shell nanoparticles showed multimodal imaging features including computed tomography (CT) (for the preliminary location of the tumor), photoacoustic (for the anatomical localization of the tumor), and fluorescence imaging (for real-time monitoring of the tumor margin) and pH- and thermal-sensitive drug release. Because the early esophageal carcinoma is a type of superficial cancer, a subcutaneous model in the thigh was used for the in vivo study. The core/shell nanoparticles shows high imaging contrast between the tumor and the adjacent tissues and controllable photothermal therapy (PTT) and chemotherapy. Our results indicated that the obtained core/shell nanoparticles had significant potential in the triple-modality imaging guided precisely chemo-thermal synergetic therapy of esophageal cancer. In addition, after aerosol administration, our nanoparticles also exhibited comparable therapeutic efficacy with the intravenous administration, which is more suitable for clinical therapy of esophageal carcinoma., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Among all the imaging techniques, ultrasound imaging has a unique advantage due to its features of real-time, low cost, high safety, and portability. Ultrasound contrast agents (UCAs) have been widely used to enhance ultrasonic signals. One of the most exciting features of UCAs for use in biomedicine is the possibility of easily putting new combinations of functional molecules into microbubbles (MBs), which are the most routinely used UCAs. Various therapeutic agents and medical nanoparticles (quantum dots, gold, Fe3O4, etc.) can be loaded into ultrasound-responsive MBs. Hence, UCAs can be developed as multifunctional agents that integrate capabilities for early detection and diagnosis and for imaging guided therapy of various diseases. The current review will focus on such state-of-the-art UCA platforms that have been exploited for multimodal imaging and for imaging guided photothermal therapy.

Theranostic microcapsules were successfully fabricated by introducing gold nanoparticles into poly(lactic acid) microcapsules through a double-microemulsion method, followed by depositing graphene oxide onto the microcapsule surface via electrostatic layer-by-layer self-assembly technique. It was proved that the obtained microcapsules could serve as a contrast agent to simultaneously enhance US imaging and X-ray CT imaging greatly both in vitro and in vivo. In addition, the in vivo therapeutic examinations showed that the microcapsule was an effective agent for photothermal therapy of cancer. The near-infrared laser light ablated the tumor completely within 9 days in the presence of the microcapsules and the tumor growth inhibition was 83.8%. The combination of real-time ultrasound with 3-D computed tomography through a single microcapsule agent is very helpful for accurately interpreting the obtained images, identifying the size and location of the tumor, as well as guiding and monitoring the photothermal therapy. Simultaneously, the effectiveness of photothermal therapy could be evaluated by the combined US and CT imaging enhanced by the microcapsule agent. Such a versatile microcapsule system might bring opportunities to the next generation of multimodal imaging guided cancer therapy., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Ultrasound (US) imaging provides a valuable opportunity to administer photothermal therapy (PTT) of cancer with real-time guidance to ensure proper targeting, but only a few theranostic agents were developed by physically grafting near infrared (NIR)-absorbing inorganic nanomaterials to ready-made ultrasound contrast agents (UCAs) for US imaging guided PTT. In this paper, NIR absorbing hollow microspheres were generated from polypyrrole merely using a facile one-step microemulsion method. It was found that the obtained polypyrrole hollow microspheres (PPyHMs) can act as an efficient theranostic agent not only to enhance US imaging greatly, but also exhibit excellent photohyperthermic effects. The contrast consistently sustained the echo signals for no less than 5 min and the NIR laser light ablated the tumor completely within two weeks in the presence of PPyHMs. More importantly, no use of additional NIR absorber substantially minimizes an onetime dose of the theranostic agent.