National Health Research Institute – Center for Nanomedicine Research

The Center for Nanomedicine Research (C-NMR) at NHRI was officially established in 2004 to coordinate and form the interdisciplinary/interdivisional research teams and to apply the nanoscience and nanotechnology to medicine, including diagnosis, therapy and prevention. The C-NMR/NHRI will also be responsible for promoting the applications of nanotechnology to medically important issues in Taiwan.

The major goals for the nanomedicine research and development activities at the NHRI is to conduct translational research from the fundamental sides (such as the the exploration of novel nano-sized materials of potential biomedical applications) to the real possible clinical applications (prevention, diagnosis and therapeutics). The major research directions for CNMR and the NHRI are: (1) nanoscience and nanotechnology in health risk assessment; (2) nanoscience and nanotechnology in medicine; and (3) nanoscience and nanotechnology in biological monitoring. Through intramural interdivisional collaboration and extramural collaborations, the CNMR/NHRI will be playing an important share of the collective efforts coordinated by the National Nanoscience Nanotechnology Program Office to promote the Nanoscience and Nanotechnology development in Taiwan.

Nanoscience and Nanotechnology in Medicine - Nanoscience in cancer (I)
Targeted Tumor Radioimmunotherapy with Radionuclide Nano-targeted Radiopharmaceuticals

To design and choose the optimal therapeutics to kill tumors with minimal systemic side effects tailored to the individual patient and early monitoring the treatment efficacy and warning of toxicity are the goals and strategies of recently advanced novel cancer therapeutics. Post genomics, the research and development of molecular imaging and targeted multifunctional therapeutics with nanotechnologies provide the opportunity to achieve these goals and conquer cancers.

The major research platform technologies of this project include nano-drug delivery technologies, molecular bio-targeted angiogenesis technologies, radiochemistry and alpha nanogenerator technologies, in vivo molecular imaging technologies. For establishment the best novel nano-targeted diagnostic and therapeutic radiopharmaceuticals to treat tumors and malignant ascites and translation from preclinical to clinical studies. New site specific passive targeted 188Re/111In/225Ac-liposome(β/γ/α radionuclides), active molecular specific targeting angiogenesis antibody radioconjugates and higher specific multivalent targeting nano-immunoliposomes will be studied, compared, and optimized from pharmacology to toxicology with murine and human animal models in the future investigations.

Fig.1.Simplified scheme for the preparation of bimodality and dual function nano-targeted radiopharmaceuticals
Fig 2 In vivo imaging of tumors and acites targeting by passive nano-targeted radiopharmaceuticals of 188Re-BMEDA-liposome and 188Re-BMEDA-Dox-liposome on C26 tumors and ascites bearing in Balb/c mice with micro-SPECT and micro-SPECT/CT

Nanoscience and Nanotechnology in Medicine - Nanotechnology in regenerative medicine (II)

Superparamagnetic iron oxide (SPIO) nanoparticles are emerging as ideal tools for noninvasive stem cell tracking. However, their low intracellular labeling efficiency has become the major problem in impeding the potential use and has evoked great interest in developing new labeling strategies. We have developed fluorescein isothiocyanate (FITC)-incorporated silica-coated core-shell SPIO, SPIO@SiO2(FITC) with diameters of 50 nm, nanoparticles as a versatile class of magnetic vectors that can efficiently label human mesenchymal stem cells (hMSCs), via clathrin- and actin-dependent endocytosis with subsequent intracellular localization in late endosomes/lysosomes. The process displays a time- and dose-dependent manner. In our system, SPIO@SiO2(FITC) nanoparticles induce sufficient MRI cell contrast at incubated doses as low as 30? mg/ml SPIO@SiO2(FITC) nanoparticles (equals to 0.5 mg iron/ml) culture medium with 1.2×105 hMSCs for 1 h, and the in vitro detection thresholds of cell numbers are about 1×104 cells. These labeled cells with 1.2×105 can also be obviously MRI detected in a subcutaneous model in vivo. Labeled hMSCs are unaffected in their viability, proliferation and differentiation capacities into adipocytes and osteocytes. In addition, these labeled cells after long-term incubation with regular growth medium or differentiation medium can still be readily MRI detected.

Fig 3 TEM images of 50 nm SPIO@SiO2(FITC) nanoparticles.
Fig 4 Animal study of core-shell IO labeled hMSCs was performed by injecting cells at the number of 1.2×104 or 1.2×105 mixed with Matrigel into subcutaneous tissue of flanks (unlabeled cells at left flank and labeled cells at right flank, respectively) of a nude mouse.
Fig 5 Sensitivity of in vitro MRI of SPIO@SiO2(FITC)-labeled hMSCs
Fig 6 Biocompatibility of GD-MSNs