Biomedical Engineering – From Theory to Applications

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218 Biomedical Engineering – From Theory to Applications change in the chemical properties of the drugs or a loss in magnetization of the core magnetic material. Second, the drug loading efficiency is not high as expected for most nano-drugs. Third, controlling the drug release at the proper compartment within the tumor is still quite challenging, since most of the loaded drugs in nanoparticles release either prematurely or at a low rate from the nanoparticles. In this regard, novel strategies such as the development of magnetic IO nanoparticles for hyperthermia treatment and heatinginduced drug release are under investigation and are expected to provide solutions for future clinical applications. 5. Conclusions and perspectives Intensive investigations and the development of magnetic IO nanoparticles in the past decade have led to the much better understanding of the biological significances and potential biomedical applications of IO nanoparticles and a wide range of novel IO nanoparticle constructs designed for tumor targeted imaging and drug delivery. However, when constructing magnetic nanoparticles for tumor imaging and drug delivery, there are several goals that remain challenging to achieve, such as 1) specific accumulation in the tumor but minimal uptake in normal tissue and organs by selecting ideal tumor-targeted ligands; 2) modification of the surface and control of the size and charge of nanoparticles for adequate delivery; 3) regulation of blood circulation time; 4) stability of IO nanotherapeutics; 5) construction of smart tumor-targeted IO nanoparticles such that loaded drugs release only within tumor cells. Recently, increasing concerns are focused on the safety of IO nanotherapeutic delivery systems. Although many animal studies have not shown visible toxicities, most of the available data come from mice with only a few studies conducted in rats, dogs and monkeys, and the sub-chronic and chronic toxicity studies for most IO nanoparticles have yet to be performed. Little is known about the long-term fate of IO nanoparticles and the pharmacokinetic/pharmacodynamic (PK/PD) changes in IO nanotherapeutics in vivo. The EPR effect constitutes only part of the drug targeting mechanism, and accumulating evidence has shown that tumor-targeted nanotherapeutics can internalize into tumor cells to a significantly higher concentration than their non-targeted counterparts. The majority of nanotherapeutic delivery systems are non-targeted, thus intensive studies using tumortargeted nanoparticles as drug delivery carriers are needed. 6. Acknowledgment This work was supported in part by grants from the National Institutes of Health (NIH), SPORE in Head & Neck Cancer (5P50CA128613-04 ), Center of Cancer Nanotechnology Excellence (CCNE, U54 CA119338-01), in vivo Cellular and Molecular Imaging Center (ICMIC, P50CA128301-01A10003) and Cancer Nanotechnology Platform Project (CCNP, 1U01CA151802-01 and 1U01CA151810-01). 7. References Abdalla, M. O., P. Karna, et al. 2010 "Enhanced noscapine delivery using uPAR-targeted optical-MR imaging trackable nanoparticles for prostate cancer therapy." J Control Release 149(3): 314-22.
Targeted Magnetic Iron Oxide Nanoparticles for Tumor Imaging and Therapy 219 Agarwal, A., U. Gupta, et al. (2009). "Dextran conjugated dendritic nanoconstructs as potential vectors for anti-cancer agent." Biomaterials 30(21): 3588-3596. Artemov, D., N. Mori, et al. (2003). "MR molecular imaging of the Her-2/neu receptor in breast cancer cells using targeted iron oxide nanoparticles." Magn Reson Med 49(3): 403-8. Atri, M. (2006). "New technologies and directed agents for applications of cancer imaging." J Clin Oncol 24(20): 3299-308. Bae, Y., T. A. Diezi, et al. (2007). "Mixed polymeric micelles for combination cancer chemotherapy through the concurrent delivery of multiple chemotherapeutic agents." J Control Release 122(3): 324-30. Bi, F., J. Zhang, et al. (2009). "Chemical conjugation of urokinase to magnetic nanoparticles for targeted thrombolysis." Biomaterials 30(28): 5125-5130. Brigger, I., C. Dubernet, et al. (2002). "Nanoparticles in cancer therapy and diagnosis." Adv Drug Deliv Rev 54(5): 631-51. Chatzistamou, L., A. V. Schally, et al. (2000). "Effective treatment of metastatic MDA- MB-435 human estrogen-independent breast carcinomas with a targeted cytotoxic analogue of luteinizing hormone-releasing hormone AN-207." Clin Cancer Res 6(10): 4158-65. Chen, H., Y. Gu, et al. (2007). "Characterization of pH- and temperature-sensitive hydrogel nanoparticles for controlled drug release." PDA J Pharm Sci Technol 61(4): 303-13. Chen, H. W., L. Y. Wang, et al. (2010). "Reducing non-specific binding and uptake of nanoparticles and improving cell targeting with an antifouling PEO-b-P gamma MPS copolymer coating." Biomaterials 31(20): 5397-5407. Chen, T. J., T. H. Cheng, et al. (2009). "Targeted Herceptin-dextran iron oxide nanoparticles for noninvasive imaging of HER2/neu receptors using MRI." J Biol Inorg Chem 14(2): 253-60. Cheng, K., S. Peng, et al. (2009). "Porous hollow Fe(3)O(4) nanoparticles for targeted delivery and controlled release of cisplatin." J Am Chem Soc 131(30): 10637-44. Cutler, J. I., D. Zheng, et al. (2010). "Polyvalent Oligonucleotide Iron Oxide Nanoparticle "Click" Conjugates." Nano Letters 10(4): 1477-1480. Daou, T. J., G. Pourroy, et al. (2006). "Hydrothermal synthesis of monodisperse magnetite nanoparticles." Chemistry of Materials 18(18): 4399-4404. Davis, M. E., Z. G. Chen, et al. (2008). "Nanoparticle therapeutics: an emerging treatment modality for cancer." Nat Rev Drug Discov 7(9): 771-82. De Palma, R., S. Peeters, et al. (2007). "Silane ligand exchange to make hydrophobic superparamagnetic nanoparticles water-dispersible." Chemistry of Materials 19(7): 1821-1831. Deshane, J., C. C. Garner, et al. (2003). "Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2." J Biol Chem 278(6): 4135-44. Gang, J., S. B. Park, et al. (2007). "Magnetic poly epsilon-caprolactone nanoparticles containing Fe3O4 and gemcitabine enhance anti-tumor effect in pancreatic cancer xenograft mouse model." J Drug Target 15(6): 445-53.
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BIOMEDICAL ENGINEERING - FROM THEOR
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120 6. Conclusion Biomedical Engine
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162 1 st phase : half year 4 2 nd p
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