台灣自1980年代起，癌症就一直位居國人十大死因之首，癌症難以治療一來是由於其生物變異程度大，二來是術後組織殘餘、沾黏都有可能再次復發，因此傳統上常同時使用手術、化療或放療等來增進其療效；其中放射治療也是很重要的一環，在早期科學家們對劑量掌控能力不佳，因此常造成病人組織潰爛死亡，但近年來隨著工藝技術與醫療技術大幅演進，放療從γ射線、電子、質子、中子演進至今日的重粒子治療等。而從1960年代開始出現的硼中子捕獲療法則是同時結合放療與藥物的一種二元治療方式，其利用含硼藥物吸收中子後核分裂產生的α粒子去摧毀腫瘤細胞，此治療方式的特點來自於含硼藥物或中子射線獨立使用時對人體的傷害十分低，且α粒子在人體內行進距離約為9μm，此距離約與一個細胞的維度相當，也意味著α粒子造成的破壞只會發生在吸收了含硼藥物的癌細胞裡，上述特點大幅提升了硼中子捕獲療法的選擇性，以現今來說治療仍受限於功能有限的含硼藥物上，因此如何合成出同時具有高濃度硼與特定選擇性的藥物是此治療未來發展性與本篇論文所要研究的重點

Cancer has been the most cause of death since 1980s in Taiwan. Traditionally, there has many treatments of cancer such as surgery, chemotherapy, radiotherapy. These therapy are directly attack to the tumor cells. Although the killing effect are very well, but they also affect the normal cells even hurt other organs in the body. And if the tumor cells were not clearly been moved from the normal tissue, it may transfer to other place and cause a newly lesions. So the scientists and doctors are looking for a more precise and effect method to kill the tumor cells. Recently, Boron Neutron Capture Therapy ( BNCT ) is a ideal option to cure the cancer.
The boron neutron capture therapy (BNCT) was started since 1936 by Locher, who suggested that two essential issues associated with BNCT: delivery of boron-10
to cancer cell and high quality and sufficient thermal neutron for irradiation. In the 1950s, Sweet started the clinical investigation on glioblastoma multiforme at Massachusetts Institute of Technology (MIT), however, 18 patients passed away from 10 days to 11.5 months after irradiation. 1960s, Hatanaka continued and modified the Sweet’s research work at Tokyo University got promising results in glioblastoma. The first time BNCT treatment in the history did not work out very well because of over-dosage. But due to the improvements of dosage-control and drug delivery system, it is much safer nowadays and become a potential therapy on advanced cancer therapy.

[1] Lawrence EO. The biological action of neutron rays. Radiology 1937; 29: 313-22.
[2] Lawrence JH, Aebersold PC, Lawrence EO. Comparative effects of X-rays and
neutrons on normal and tumor tissue. Proc Nat Acad Sci USA 1936; 22: 543.
[3] Lochner GL. Biological effects and therapeutic possibilities of neutrons. Am J
Roentgenol Radiat Ther 1936; 36: 1-13.
[4] Barth RF, Joensnu H. Boron neutron capture therapy for the treatment of
glioblastomas and extracranial tumours: as effective, more effective or less effective than photon irradiation? Radiother Oncol 2007; 82 : 119 – 22.
[5] Sweet WH. Early history of development of boron neutron capture therapy of tumors. J Neurooncol 1997; 33: 19-26.
[6] Edward C Halperin. Particle therapy and treatment of cancer. Lancet Oncol 2006; 7: 676–85
[7] Nakagawa Y, Hatanaka H. Boron neutron capture therapy: clinical brain tumor studies. J Neurooncol 1997; 33: 105-15.
[8] Wang LW, Wang SJ, Chu PY, Ho CY, Jiang SH, Liu YW, Liu YH, Liu HM, Peir JJ, Chou FI, et al: BNCT for locally recurrent head and neck cancer: preliminary clinical experience from a phase I/II trial at Tsing-Hua open-pool reactor. Appl Radiat Isot 2011; 69: 1803-1806.
[9] Gray LH. Comparative studies of the biological effects of x-rays, neutrons and other ionizing radiations. Brit Med Bull 1946; 4: 11-18.
[10] Mottram JC. Skin reaction to radium exposure and their avoidance in therapy; an experimental investigation. Brit J Radiol 1924; 29: 174–80.
[11] Crabtree HG, Cramer W. The action of radium on cancer cells I— effects of
~ 43 ~
hydrocyanic acid, iodo-Acetic acid, and sodium fluoride on the metabolism and transplantability of cancer cells. Proc R Soc Lond B Biol Sci 1933; 113: 226–38.
[12] Crabtree HG, Cramer W. Action of radium on cancer cells: some factors affecting the susceptibility of cancer cells to radium. Proc R Soc Lond B Biol Sci 1933; 113: 226–38.
[13] Mottram JC. Factors of importance in radiosensitivity of tumors. Br J Radiol 1936; 9: 606–14.
[14] Thomlinson RH, Gray LH. The histologic structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 1955; 9: 539-549.
[15] Fowler JF, Morgan RL. Pre-therapeutic experiments with the fast neutron beam from the medical research council cyclotron, VIII : general review. Br J Radiol 1963; 36: 115–21.
[16] Raju MR. Particle radiotherapy: historical developments and current status. Radiat Res 1996; 145: 391–407.
[17] Bewley DK. Field SB, Morgan RL, et al. The response of pig skin to fractionated treatments with fast neutrons and x-rays. Br J Radiol 1967; 40: 765–70.
[18] Rolf F Barth, M Graca H Vicente, Otto K Harling, W S Kiger III, Kent J Riley,
Peter J Binns, Franz M Wagner, Minoru Suzuki, Teruhito Aihara, Itsuro Kato and Shinji Kawabata : Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer. Radiation Oncology 2012; 7: 146.
[19] Rosenthal MA, Kavar B, Hill JS et al, Phase I and pharmacokinetic study of photodynamic therapy for high-grade gliomas using a novel boronated porphyrin. J Clin Oncol 2001; 19: 519-524.
[20] Shukla S, Wu G, Chatterjee M et al, Synthesis and biological evaluation of folate
~ 44 ~
receptor-targeted boronated pamam dendrimers as potential agents for neutron capture therapy. Bioconjug Chem 2003; 14: 158-167.
[21] Yinghuai Z, Peng A, Carpenter K et al, Substituted carborane-appended water-soluble single-wall carbon nanotubes: new approach to boron neutron capture therapy drug delivery. J Am Chem Soc 2005; 127: 9875-9880.
[22] Suzuki M, Sakurai Y, Masunaga S et al, Study of boron neutron capture therapy with borocaptate sodium (BSH)/lipiodol emulsion (BSH/lipiodol-BNCT) for treatment of multiple liver tumors. Int J Radiat Oncol Biol Phys 2003; 58: 892-896.
[23] Suzuki M, Nagata K, Masunaga S et al, Biodistribution of 10B in a rat liver tumor model following intra-arterial administration of sodium borocaptate (BSH) / degradable starch microspheres (DSM) emulsion. Appl Radiat Isot 2004; 61: 933-937.
[24] Ynagie H, Tomita T, Kobayashi H et al, Application of boronated anti-cea immunoliposome to tumor cell growth inhibition in vitro boron neutron capture therapy model. Br J cancer 1991; 63: 522-526.
[25] Pan XQ, Wang H, Shukla S et al, Introductory experiments on ligand liposomes as potential delivery agents for neutron capture therapy. Bioconjug Chem 2003; 13: 435-442.
[26] Feakes DA, Shelly K, Hawthornet MF, Selective boron delivery to murine tumors by lipophilic species incorporated in the membranes of unilamellar lipsomes. Proc Natl Acad Sci USA 1995; 92: 1367-1370.
[27] Nakamura H, Miyajima Y, Takei T et al., Synthesis and vesicle formation of a nido-carborane cluster lipid for boron neutron capture therapy. Chem Commun 2004; 1910-1911.
~ 45 ~
[28] Li T, Hamdi J, Hawthrone MF, Unilamellar liposomes with enhanced boron content. Bioconjug Chem 2006; 17: 15-20.
[29] Lee J-D, Ueno M, Miyajima Y, Nakamura H, Synthesis of boron cluster lipids: closo-Dodecaborate as an alternate hydrophilic function of boronated liposomes for neutron capture therapy. Org Lett 2007; 9: 323-326.
[30] Nakamura H, Lee J-D, Ueno M, Miyajima Y, Ban HS, Synthesis of closo-dodecaboryl lipids and their liposomal formation for boron neutron capture therapy. NanoBiotechnology 2008; 3: 135-145.
[31] Nakamura H, Ueno M, Ban HS et al, Development of boron nano capsules for neutron capture therapy. Appl Radiat Isot 2009; 67: S84-S87.
[32] Justus E, Awad D, Hohnholt M et al, Synthesis, liposomal preparation and in vitro toxicity of two novel dodecaborate cluster lipids for boron neutron capture therapy. Bioconjug Chem 2007; 18: 1287-1293.
[33] Feakes DA, Spinler JK, Harris FR, Synthesis of boron-containing cholesterol derivatives for incorporation into unilamellar liposomes and evaluation as potential agents for BNCT. Tetrahedron 1999; 55: 11177-11186.
[34] Nakamura H, Ueno M, Lee JD et al, Synthesis of dodecaborate-conjugated cholesterols for efficient boron delivery in neutron capture therapy. Tetrahedron Lett 2007; 48: 3151-3154.
[35] Griffith LG. Polymeric biomaterials. Acta Mater 2000; 48: 263–77.
[36] Lampe KJ, Namba RM, Silverman TR, Bjugstad KB, Mahoney MJ. Impact of lactic acid on cell proliferation and free radical-induced cell death in monolayer cultures of neural precursor cells. Biotechnol Bioeng 2009; 103: 1214–23.
[37] Auras R, Lim LT, Selke SEM, Tsuji H. Poly(lactic acid): synthesis, structures, properties, processing, and application. New Jersey: Jhon Wiley & Sons, Inc;
~ 46 ~
2010.
[38] Auras R, Lim LT, Selke SEM, Tsuji H. Poly(lactic acid): synthesis, structures, properties, processing, and application. New Jersey: Jhon Wiley & Sons, Inc; 2010.
[39] Auras R, Harte B, Selke S. An overview of polylactides as packaging materials. Macromol Biosci 2004; 4: 835–864.
[40] Bleach NC, Tanner KE, Kellomäki M, Törmälä P. Effect of filler type on the mechanical properties of self-reinforced polylactide-calcium phosphate composites. J Mater Sci Mater Med 2001; 12: 911–915.
[41] Cha Y, Pitt CG. The biodegradability of polyester blends. Biomater 1990; 11: 108–112.
[42] Drumright RE, Gruber PR, Henton DE. Polylactic acid technology. Adv Mater 2000; 12: 1841–1846.
[43] Tsuji H, Ishida T. Poly(L-lactide).X. Enhanced surface hydrophilicity and chain scission mechanisms of poly(L-lactide) film in enzymatic, alkaline, and phosphate-buffered solutions. J Appl Polym Sci 2003; 87: 1628–1633.
[44] Middleton JC, Tipton AJ. Synthetic biodegradable polymers as orthopedic devices. Biomaterial 2000; 21: 2335–2346.
[45] Gupta B, Revagade N, Hilborn J. Poly(lactic acid) fiber: an overview. Prog Polym Sci 2007; 34: 455–482.
[46] Yamane H, Sasai K. Effect of the addition of poly(D-lactic acid) on the thermal property of poly(L-lactic acid). Polymer 2003; 44: 2569–2575.
[47] Drumright RE, Gruber PR, Henton DE. Polylactic acid technology. Adv Mater 2000; 12: 1841–1846.
[48] Cheng Y, Deng S, Chen P, Ruan R. Polylactic acid (PLA) synthesis and
~ 47 ~
modifications: a review. Front Chem China 2009; 4: 259–264.
[49] Gupta B, Revagade N, Hilborn J. Poly(lactic acid) fiber: an overview. Prog Polym Sci 2007; 34: 455–482.
[50] Durselen L, Dauner M, Hierlemann H, Planck H, Claes LE, Ignatius A.
Resorbable polymer fibers for ligament augmentation. J Biomed Mater Res
2001; 58: 666–672.
[51] Coutu DL, Yousefi AM, Galipeau J. Three-dimensional porous scaffolds at the
Crossroads of tissue engineering and cell-based gene therapy. J Cell Biochem
2009; 108: 537–546.
[52] Kellomäki M, Niiranen H, Puumanen K, Ashammakhi N, Waris T, Törmäla P.
Bioabsorbable scaffolds for guided bone regeneration and generation. Biomater
2000; 21: 2495–2505.
[53] Papenburg BJ, Liu J, Higuera G, Barradas AMC, Boer J, Blitterswijk VCA, et
al. Development and analysis of multi-layer scaffolds for tissue engineering.
Biomater 2009; 30: 6228–6239.
[54] Valantin MA, Aubron-Olivier C, Ghosn J, Laglenne E, Pauchard M, Schoen H, et al. Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study. AIDS 2003; 17: 2471–2477.
[55] Vanessa Geis, Kristin Guttsche, Carsten Knapp, Harald Scherer, Rabiya Uzun : Synthesis and characterization of synthetically useful salts of the
weakly-coordinating dianion [B12Cl12]2- . Dalton Trans. 2009; 2687–2694.
[56] Unpublished method was offered by Andrey, Nuclear Science Center, Russia.
[57] The synthsis of PLA-OH, PLA-mesylate, PLA-PEOz-NH2 are all provided by Ph.D. Wen-Yuan Hsieh, Industrial Technology Research Institute, Taiwan.