Applications, opportunities and challenges of molecular probes in the diagnosis and treatment of major diseases

Minimally invasive treatment of cancer can significantly reduce surgery risks due to many advantages, such as no laparotomy, small wound and early recovery and so on. Especially, it is suitable for patients who cannot be operated on due to tumor distant metastasis, oldness, weakness, and major organ dysfunction. According to clinical statistics, more than 60% of patients with mid-advanced cancer can be cured by employing minimally invasive surgery. Malignant tumors often show invasive growth and unclear boundary, resulting in partial removal of healthy tissue during surgery, hence postoperative sequelae and dysfunction. In order to carry out minimally invasive surgery and targeted elimination of tumor, the size and location of the tumors must be accurately identified before therapy, which requires the imaging guidance. By using optical molecular imaging, we can find a small tumor less than ~1mm. Therefore, the molecular imaging navigation provides a great opportunity for the development of minimally invasive interventional therapy for cancer. Especially, the cancer specific probes are emerging as one of the key technologies of molecular imaging. Compared with small molecular probes, nanoprobes show longer imaging time, remarkable signal multiplication and drug loading capacity. There, specific nanoprobes become the development direction of the molecular imaging navigation technology. Aiming at accuracy, high efficacy and minimal invasiveness of cancer treatments, we need solve two key scientific issues including identification of tumor boundary and predictability of lymph node metastases, and develop three key technologies including: high accumulation of nanoprobes at tumor sites, high sensitivity of nanoprobes to cancer cells, high precision imaging methods based on nanoprobes. This project will design and construct a variety of safe and efficient nanoprobes and related nanomaterials with independent intellectual property rights. For example, ultra pH (or enzyme)-sensitive fluorescent nanoprobes will be fabricated for the imaging of a broad range of tumours by nonlinear amplification of microenvironment signals. Multifunctional nanoprobes will be developed for simultaneous molecular imaging and interventional therapy of cancer. Fluorescent/ultrasound nanoprobes will be prepared to achieve a bimodal imaging with excellent signal sensitivity and high spatial resolution. Theranostic nanoprobes will be produced for both targeted imaging (diagnosis) and interventional therapy (laser, ultrasound, microwave, radiofrequency or combination etc.). In addition, we will establish a practical and feasible technology platform for large-scale production of nanoprobes, and in vivo and in vitro evaluation systems for the clinical applications of nanoprobes. It is of crucial importance to investigate the biological influence of nanoprobes on cell division, proliferation, apoptosis and signal transduction pathways, assess in vivo transport mechanism across biological barriers, and evaluate biosafety of nanoprobes, such as acute toxicity, long-term toxicity, nervous system toxicity and immunogenicity. Moreover, fluorescence confocal microendoscope and minimally invasive therapeutic devices will be developed based on nanoprobes. Finally, we will assess invasion depth and lymph node metastasis in early gastric cancer, as well as retroperitoneal lymph node metastasis of ovarian cancer by using nanoprobes in combination of fluorescence confocal microendoscope and molecular imaging navigation system. The sensitivity and specificity of molecular imaging nanoprobes are evaluated by using pathology as the gold standard. The precise interventional therapy (photodynamic, photothermal and sonodynamic etc.) will be implemented by irradiating the tumor tissue using laser or ultrasound under the guidance of nanoprobe-enhanced molecular imaging. It is essential to investigate the evaluation methods of therapeutic efficacy. We will explore the synergistic, anti-metastatic and overcoming drug resistance effects of interventional therapy combined with chemotherapy. In conclusion, molecular imaging nanoprobes can be used not only for imaging and diagnosis, but also for the minimally invasive interventional treatments. In particular, the research and application of nanoprobes will promote the development and application of fluorescence confocal microendoscope, molecular imaging navigation systems and minimally invasive interventional therapy systems. This will accelerate the breakthrough in the key technology of major medical equipment. Undoubtedly, the accomplishment of the project would enhance the innovation capability and international competitiveness of China in nanobiomedicine and medical equipment.