以材料製備鑑定、in tube 實驗及初步 in vitro 實驗分別進行探討。
此熱敏感性的 PLG-SPIONs nanoshuttles 其粒徑大小約為 260 nm 及界達電為值 約為-55 mV，確實符合藥物傳遞系統的尺度且是個穩定的膠體溶液系統，然而 TEM 結果圖可以發現 PLG-SPIONs nanoshuttles 內所包覆的 SPIONs 數量可能略少，導 致 MRI T2 顯影效果不夠顯著，所以這部分的實驗方法有待未來調整至最佳化。既 然 PLG-SPIONs nanoshuttles 的 gel core 是熱敏感性材料所組成，由 DSC 測得相變
溫度得約為 44oC，確實落在溫熱治療溫度範圍內。
以直接加熱的釋放曲線圖可以觀察出，在 45oC 能有效地釋放藥物，但由於實
驗時間不夠久，所以有待未來做更長的時間，去探究之後的釋放狀況是不是會到 達飽和點。初步實驗證實，施予高頻率電磁場(frequency : 33.9 kHz, H : 33.9 kA/m) 後，PLG-SPIONs nanoshuttles 確實有優良的升溫效果其 SLP 值為 369 W/gFe，所以 未來也需要做一組以電磁生熱的方式其藥物釋放曲線圖，去探討其釋放模式與效 率是否比直接加熱法更有效也有待確認。
經過初步 in vitro 實驗證實，PLG-SPIONs nanoshuttles 無細胞毒性，且包覆喜 樹鹼之 PLG-CPT/SPIONs nanoshuttles 對癌細胞的毒殺能力較 free drug CPT 強，未 來需證明經過啟動外部電磁場後，PLG-CPT/SPIONs nanoshuttles 確實結合化學藥 物治療及溫熱治療強化了毒殺癌細胞的有效性，並且此熱敏感載體應可在 in vivo 模式中被再次證實其化療及溫熱治療之協同效應。
56
參考文獻
(1)
http://www.doh.gov.tw/CHT2006/DM/DM2_p01.aspx?class_no=25&level_no=1
&doc_no=84788 (Accessed July, 2003)
(2) Neil, B. G. Polymeric Inserts and Implants for the Controlled Release of Drugs. British Polymer Journal 1978, 10, 260-266.
(3) Alekha, K. D.; Greggrey, C. C. Therapeutic applications of implantable drug delivery systems. Journal of Pharmacological and Toxicological Methods 1998, 40.
(4) Skeel, R. T.; Khleif, S. N. Handbook of cancer chemotherapy. Lippincott Williams & Wilkins 2011.
(5) Peer, D.; Karp, J.; Hong, S.; Farokhzad, O.; Margalit, R.; Langer, R.
Nanocarriers as an emerging platform for cancer therapy. Nature nanotechnology 2007, 2, 751-760.
(6) Matsumura, Y.; Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer research 1986, 46, 6387-6392.
(7) Yallapu, M.; Jaggi, M.; Chauhan, S. Scope of nanotechnology in ovarian cancer therapeutics. Journal of ovarian research 2010, 3, 19.
(8) Alexis, F.; Pridgen, E.; Langer, R.; Farokhzad, O. Nanoparticle technologies for cancer therapy. Handbook of experimental pharmacology 2010, 55-86.
(9) Albanese, A.; Tang, P.; Chan, W. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annual review of biomedical engineering 2012, 14, 1-16.
(10) Petros, R.; DeSimone, J. Strategies in the design of nanoparticles for therapeutic applications. Nature reviews. Drug discovery 2010, 9, 615-627.
(11) MacEwan, S.; Callahan, D.; Chilkoti, A. Stimulus-responsive macromolecules and nanoparticles for cancer drug delivery. Nanomedicine 2010, 5, 793-806.
(12) Cervadoro, A.; Giverso, C.; Pande, R.; Sarangi, S.; Preziosi, L.; Wosik, J.;
Brazdeikis, A.; Decuzzi, P. Design maps for the hyperthermic treatment of tumors with superparamagnetic nanoparticles. PloS one 2013, 8, e57332.
(13) Mahmoudi, M.; Sant, S.; Wang, B.; Laurent, S.; Sen, T. Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy. Advanced drug delivery reviews 2011, 63, 24-46.
57
(14) Farokhzad, O.; Langer, R. Impact of nanotechnology on drug delivery. ACS nano 2009, 3, 16-20.
(15) Ozcelikkale, A.; Ghosh, S.; Han, B. Multifaceted Transport Characteristics of Nanomedicine: Needs for Characterization in Dynamic Environment. Molecular
pharmaceutics 2013, 10, 2111-2126.
(16) Cho, K.; Wang, X.; Nie, S.; Chen, Z.; Shin, D. Therapeutic nanoparticles for drug delivery in cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 2008, 14, 1310-1316.
(17) Barenholz, Y. Doxil®--the first FDA-approved nano-drug: lessons learned.
Journal of controlled release : official journal of the Controlled Release Society 2012, 160, 117-134.
(18) Gabizon, A.; Catane, R.; Uziely, B.; Kaufman, B.; Safra, T.; Cohen, R.;
Martin, F.; Huang, A.; Barenholz, Y. Prolonged circulation time and enhanced
accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer research 1994, 54, 987-992.
(19) Wall, M. E.; Wani, M. C.; Cook, C. E.; Palmer, K. H.; McPhail, A. T.; Sim, G.
A. Plant Antitumor Agents. I. The Isolation and Structure of Camptothecin, a Novel Alkaloidal Leukemia and Tumor Inhibitor from Camptotheca acuminata1,2. Journal of the American Chemical Society 1966, 88, 3888-3890.
(20) Hsiang, Y.; Liu, L.; Wall, M.; Wani, M.; Nicholas, A.; Manikumar, G.;
Kirschenbaum, S.; Silber, R.; Potmesil, M. DNA topoisomerase I-mediated DNA cleavage and cytotoxicity of camptothecin analogues. Cancer research 1989, 49, 4385-4389.
(21) Hsiang, Y.; Hertzberg, R.; Hecht, S.; Liu, L. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. The Journal of biological chemistry 1985, 260, 14873-14878.
(22) Langer, R. Drug delivery and targeting. Nature 1998, 392, 5-10.
(23) Moon, W.; Lin, Y.; O'Loughlin, T.; Tang, Y.; Kim, D.-E.; Weissleder, R.;
Tung, C.-H. Enhanced tumor detection using a folate receptor-targeted near-infrared fluorochrome conjugate. Bioconjugate chemistry 2003, 14, 539-545.
(24) Liu, L.; Zheng, M. Y.; Renette, T.; Kissel, T. Modular Synthesis of Folate Conjugated Ternary Copolymers:
Polyethylenimine-graft-Polycaprolactone-block-Poly(ethylene glycol)-Folate for Targeted Gene Delivery. Bioconjugate chemistry 2012, 23, 1211-1220.
(25) Delehanty, J.; Boeneman, K.; Bradburne, C.; Robertson, K.; Bongard, J.;
58
Medintz, I. Peptides for specific intracellular delivery and targeting of nanoparticles:
implications for developing nanoparticle-mediated drug delivery. Therapeutic delivery
2010, 1, 411-433.
(26) Ishida, O.; Maruyama, K.; Tanahashi, H.; Iwatsuru, M.; Sasaki, K.; Eriguchi, M.; Yanagie, H. Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors in vivo. Pharmaceutical research
2001, 18, 1042-1048.
(27) Derycke, A.; De Witte, P. Transferrin-mediated targeting of hypericin embedded in sterically stabilized PEG-liposomes. International journal of oncology
2002, 20, 181-187.
(28) Brekken, R.; Overholser, J.; Stastny, V.; Waltenberger, J.; Minna, J.; Thorpe, P. Selective inhibition of vascular endothelial growth factor (VEGF) receptor 2
(KDR/Flk-1) activity by a monoclonal anti-VEGF antibody blocks tumor growth in mice. Cancer research 2000, 60, 5117-5124.
(29) Maxfield, F.; McGraw, T. Endocytic recycling. Nature reviews. Molecular cell biology 2004, 5, 121-132.
(30) Wileman, T.; Harding, C.; Stahl, P. Receptor-mediated endocytosis.
Biochemical Journal 1985, 232, 1-14.
(31) Allen, T. Ligand-targeted therapeutics in anticancer therapy. Nature reviews.
Cancer 2002, 2, 750-763.
(32) Parker, N.; Turk, M.; Westrick, E.; Lewis, J.; Low, P.; Leamon, C. Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Analytical biochemistry 2005, 338, 284-293.
(33) Lu, Y. J.; Low, P. S. Folate-mediated delivery of macromolecular anticancer therapeutic agents. Advanced drug delivery reviews 2002, 54, 675-693.
(34) Nakashima-Matsushita, N.; Homma, T.; Yu, S.; Matsuda, T.; Sunahara, N.;
Nakamura, T.; Tsukano, M.; Ratnam, M.; Matsuyama, T. Selective expression of folate receptor beta and its possible role in methotrexate transport in synovial macrophages from patients with rheumatoid arthritis. Arthritis and rheumatism 1999, 42, 1609-1616.
(35) Henderson, G.; Tsuji, J.; Kumar, H. Mediated uptake of folate by a high-affinity binding protein in sublines of L1210 cells adapted to nanomolar concentrations of folate. The Journal of membrane biology 1988, 101, 247-258.
(36) Luhrs, C.; Sadasivan, E.; da Costa, M.; Rothenberg, S. The isolation and properties of multiple forms of folate binding protein in cultured KB cells. Archives of biochemistry and biophysics 1986, 250, 94-105.
59
(37) Kane, M.; Elwood, P.; Portillo, R.; Antony, A.; Najfeld, V.; Finley, A.;
Waxman, S.; Kolhouse, J. Influence on immunoreactive folate-binding proteins of extracellular folate concentration in cultured human cells. The Journal of clinical investigation 1988, 81, 1398-1406.
(38) Low, P.; Antony, A. Folate receptor-targeted drugs for cancer and inflammatory diseases. Advanced drug delivery reviews 2004, 56, 1055-1058.
(39) Low, P.; Henne, W.; Doorneweerd, D. Discovery and development of
folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Accounts of chemical research 2008, 41, 120-129.
(40) Sudimack, J.; Lee, R. Targeted drug delivery via the folate receptor. Advanced drug delivery reviews 2000, 41, 147-162.
(41) Reddy, J.; Low, P. Folate-mediated targeting of therapeutic and imaging agents to cancers. Critical reviews in therapeutic drug carrier systems 1998, 15, 587-627.
(42) Wadajkar, A.; Menon, J.; Tsai, Y.-S.; Gore, C.; Dobin, T.; Gandee, L.;
Kangasniemi, K.; Takahashi, M.; Manandhar, B.; Ahn, J.-M.; Hsieh, J.-T.; Nguyen, K.
Prostate cancer-specific thermo-responsive polymer-coated iron oxide nanoparticles.
Biomaterials 2013, 34, 3618-3625.
(43) Sonvico, F.; Mornet, S.; Vasseur, S.; Dubernet, C.; Jaillard, D.; Degrouard, J.;
Hoebeke, J.; Duguet, E.; Colombo, P.; Couvreur, P. Folate-conjugated iron oxide nanoparticles for solid tumor targeting as potential specific magnetic hyperthermia mediators: synthesis, physicochemical characterization, and in vitro experiments.
Bioconjugate chemistry 2005, 16, 1181-1188.
(44) Ting-Yu, L.; Shang-Hsiu, H.; Dean-Mo, L.; San-Yuan, C.; Chen, I. W.
Biomedical nanoparticle carriers with combined thermal and magnetic responses. Nano Today 2009, 4, 52-65.
(45) Qiu, Y.; Park, K. Environment-sensitive hydrogels for drug delivery.
Advanced drug delivery reviews 2012, 64, 49-60.
(46) Timko, B.; Dvir, T.; Kohane, D. Remotely triggerable drug delivery systems.
Advanced Materials 2010, 22, 4925-4943.
(47) Prow, T.; Grice, J.; Lin, L.; Faye, R.; Butler, M.; Becker, W.; Wurm, E.;
Yoong, C.; Robertson, T.; Soyer, H.; Roberts, M. Nanoparticles and microparticles for skin drug delivery. Advanced drug delivery reviews 2011, 63, 470-491.
(48) Park, M.; Joo, M.; Choi, B.; Jeong, B. Biodegradable thermogels. Accounts of chemical research 2012, 45, 424-433.
60
(49) D'Souza, G.; Wagle, M.; Saxena, V.; Shah, A. Approaches for targeting mitochondria in cancer therapy. Biochimica et biophysica acta 2011, 1807, 689-696.
(50) Cui, W.; Lu, X.; Cui, K.; Niu, L.; Wei, Y.; Lu, Q. Dual-responsive controlled drug delivery based on ionically assembled nanoparticles. Langmuir : the ACS journal of surfaces and colloids 2012, 28, 9413-9420.
(51) Comenge, J.; Sotelo, C.; Romero, F.; Gallego, O.; Barnadas, A.; Parada, T.;
Domínguez, F.; Puntes, V. Detoxifying antitumoral drugs via nanoconjugation: the case of gold nanoparticles and cisplatin. PloS one 2012, 7, e47562.
(52) Zhang, W.; Gilstrap, K.; Wu, L.; K C, R.; Moss, M.; Wang, Q.; Lu, X.; He, X.
Synthesis and characterization of thermally responsive Pluronic F127-chitosan
nanocapsules for controlled release and intracellular delivery of small molecules. ACS nano 2010, 4, 6747-6759.
(53) Zhang, H.; Zhao, C.; Cao, H.; Wang, G.; Song, L.; Niu, G.; Yang, H.; Ma, J.;
Zhu, S. Hyperbranched poly(amine-ester) based hydrogels for controlled multi-drug release in combination chemotherapy. Biomaterials 2010, 31, 5445-5454.
(54) Wei, L.; Cai, C.; Lin, J.; Chen, T. Dual-drug delivery system based on hydrogel/micelle composites. Biomaterials 2009, 30, 2606-2613.
(55) Thévenot, J.; Oliveira, H.; Sandre, O.; Lecommandoux, S. Magnetic responsive polymer composite materials. Chemical Society reviews 2013, 10.1039/c3cs60058k.
(56) Jeong, B.; Bae, Y.; Lee, D.; Kim, S. Biodegradable block copolymers as injectable drug-delivery systems. Nature 1997, 388, 860-862.
(57) Chung, J.; Yokoyama, M.; Okano, T. Inner core segment design for drug delivery control of thermo-responsive polymeric micelles. Journal of controlled release : official journal of the Controlled Release Society 2000, 65, 93-103.
(58) Alkilany, A.; Thompson, L.; Boulos, S.; Sisco, P.; Murphy, C. Gold nanorods:
their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions. Advanced drug delivery reviews 2012, 64, 190-199.
(59) Rai, P.; Mallidi, S.; Zheng, X.; Rahmanzadeh, R.; Mir, Y.; Elrington, S.;
Khurshid, A.; Hasan, T. Development and applications of photo-triggered theranostic agents. Advanced drug delivery reviews 2010, 62, 1094-1124.
(60) Berg, K.; Moan, J. Lysosomes and microtubules as targets for
photochemotherapy of cancer. Photochemistry and photobiology 1997, 65, 403-409.
(61) Agostinis, P.; Berg, K.; Cengel, K.; Foster, T.; Girotti, A.; Gollnick, S.; Hahn,
61
S.; Hamblin, M.; Juzeniene, A.; Kessel, D.; Korbelik, M.; Moan, J.; Mroz, P.; Nowis, D.;
Piette, J.; Wilson, B.; Golab, J. Photodynamic therapy of cancer: an update. CA: a cancer journal for clinicians 2011, 61, 250-281.
(62) Berg, K.; Selbo, P.; Prasmickaite, L.; Tjelle, T.; Sandvig, K.; Moan, J.;
Gaudernack, G.; Fodstad, O.; Kjølsrud, S.; Anholt, H.; Rodal, G.; Rodal, S.; Høgset, A.
Photochemical internalization: a novel technology for delivery of macromolecules into cytosol. Cancer research 1999, 59, 1180-1183.
(63) Davis, M.; Chen, Z.; Shin, D. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nature reviews. Drug discovery 2008, 7, 771-782.
(64) La Belle, M.; Blanche, P.; Krauss, R. Charge properties of low density lipoprotein subclasses. Journal of lipid research 1997, 38, 690-700.
(65) Masoud, H.; Alexeev, A. Controlled release of nanoparticles and macromolecules from responsive microgel capsules. ACS nano 2012, 6, 212-219.
(66) Han, Y.; Shchukin, D.; Yang, J.; Simon, C.; Fuchs, H.; Möhwald, H.
Biocompatible protein nanocontainers for controlled drugs release. ACS nano 2010, 4, 2838-2844.
(67) Gupta, P.; Vermani, K.; Garg, S. Hydrogels: from controlled release to pH-responsive drug delivery. Drug discovery today 2002, 7, 569-579.
(68) Gao, Y.; Chen, Y.; Ji, X.; He, X.; Yin, Q.; Zhang, Z.; Shi, J.; Li, Y.
Controlled intracellular release of doxorubicin in multidrug-resistant cancer cells by tuning the shell-pore sizes of mesoporous silica nanoparticles. ACS nano 2011, 5, 9788-9798.
(69) Douglas, S.; Davis, S.; Illum, L. Nanoparticles in drug delivery. Critical reviews in therapeutic drug carrier systems 1987, 3, 233-261.
(70) Doane, T.; Burda, C. The unique role of nanoparticles in nanomedicine:
imaging, drug delivery and therapy. Chemical Society reviews 2012, 41, 2885-2911.
(71) Diebold, Y.; Jarrín, M.; Sáez, V.; Carvalho, E.; Orea, M.; Calonge, M.; Seijo, B.; Alonso, M. Ocular drug delivery by liposome-chitosan nanoparticle complexes (LCS-NP). Biomaterials 2007, 28, 1553-1564.
(72) Dicheva, B.; Hagen, T.; Li, L.; Schipper, D.; Seynhaeve, A.; Rhoon, G.;
Eggermont, A. M.; Lindner, L.; Koning, G. Cationic Thermosensitive Liposomes: A Novel Dual Targeted Heat-Triggered Drug Delivery Approach for Endothelial and Tumor Cells. Nano letters 2013, 13, 2324-2331.
(73) Chirra, H.; Desai, T. Emerging microtechnologies for the development of oral drug delivery devices. Advanced drug delivery reviews 2012, 64, 1569-1578.
62
(74) Chen, K.-J.; Liang, H.-F.; Chen, H.-L.; Wang, Y.; Cheng, P.-Y.; Liu, H.-L.;
Xia, Y.; Sung, H.-W. A thermoresponsive bubble-generating liposomal system for triggering localized extracellular drug delivery. ACS nano 2013, 7, 438-446.
(75) Dicheva, B. M.; Hagen, T. L.; Li, L.; Schipper, D.; Seynhaeve, A. L.; Rhoon, G. C.; Eggermont, A. M.; Lindner, L. H.; Koning, G. A. Cationic Thermosensitive Liposomes: A Novel Dual Targeted Heat-Triggered Drug Delivery Approach for Endothelial and Tumor Cells. Nano Lett 2013, 13, 2324 - 2331.
(76) Zhang, Z.; Cao, W.; Jin, H.; Lovell, J.; Yang, M.; Ding, L.; Chen, J.; Corbin, I.; Luo, Q.; Zheng, G. Biomimetic nanocarrier for direct cytosolic drug delivery.
Angewandte Chemie (International ed. in English) 2009, 48, 9171-9175.
(77) Zhang, J.; Sun, H.; Ma, P. Host-guest interaction mediated polymeric
assemblies: multifunctional nanoparticles for drug and gene delivery. ACS nano 2010, 4, 1049-1059.
(78) Yan, Y.; Johnston, A.; Dodds, S.; Kamphuis, M.; Ferguson, C.; Parton, R.;
Nice, E.; Heath, J.; Caruso, F. Uptake and intracellular fate of disulfide-bonded polymer hydrogel capsules for Doxorubicin delivery to colorectal cancer cells. ACS nano 2010, 4, 2928-2936.
(79) Vogel, B.; Mallapragada, S. Synthesis of novel biodegradable polyanhydrides containing aromatic and glycol functionality for tailoring of hydrophilicity in controlled drug delivery devices. Biomaterials 2005, 26, 721-728.
(80) Stuart, M.; Huck, W.; Genzer, J.; Müller, M.; Ober, C.; Stamm, M.;
Sukhorukov, G.; Szleifer, I.; Tsukruk, V.; Urban, M.; Winnik, F.; Zauscher, S.; Luzinov, I.; Minko, S. Emerging applications of stimuli-responsive polymer materials. Nature materials 2010, 9, 101-113.
(81) Samarajeewa, S.; Shrestha, R.; Li, Y.; Wooley, K. Degradability of
poly(lactic acid)-containing nanoparticles: enzymatic access through a cross-linked shell barrier. Journal of the American Chemical Society 2012, 134, 1235-1242.
(82) Nam, K.; Nam, H.; Kim, P.-H.; Kim, S. Paclitaxel-conjugated PEG and arginine-grafted bioreducible poly (disulfide amine) micelles for co-delivery of drug and gene. Biomaterials 2012, 33, 8122-8130.
(83) Glen, S. K.; Kazunori, K. Block copolymer micelles as long-circulating drug vehicles. Advanced drug delivery reviews 1995, 16, 295-309.
(84) Cheng, Y.; Hao, J.; Lee, L.; Biewer, M.; Wang, Q.; Stefan, M. Thermally controlled release of anticancer drug from self-assembled γ-substituted amphiphilic poly(ε-caprolactone) micellar nanoparticles. Biomacromolecules 2012, 13, 2163-2173.
63
(85) Chen, Y.; Liu, L. Modern methods for delivery of drugs across the blood-brain barrier. Advanced drug delivery reviews 2012, 64, 640-665.
(86) Chen, W.; Cheng, Y.; Wang, B. Dual-responsive boronate crosslinked micelles for targeted drug delivery. Angewandte Chemie (International ed. in English)
2012, 51, 5293-5295.
(87) Wu, X.-Y.; Huang, S.-W.; Zhang, J.-T.; Zhuo, R.-X. Preparation and characterization of novel physically cross-linked hydrogels composed of poly(vinyl alcohol) and amine-terminated polyamidoamine dendrimer. Macromolecular bioscience
2004, 4, 71-75.
(88) Prankerd, R.; Stella, V. The use of oil-in-water emulsions as a vehicle for parenteral drug administration. Journal of parenteral science and technology : a publication of the Parenteral Drug Association 1990, 44, 139-149.
(89) Sau, T.; Murphy, C. Seeded high yield synthesis of short Au nanorods in aqueous solution. Langmuir : the ACS journal of surfaces and colloids 2004, 20, 6414-6420.
(90) Ip, S.; MacLaughlin, C.; Gunari, N.; Walker, G. Phospholipid membrane encapsulation of nanoparticles for surface-enhanced Raman scattering. Langmuir : the ACS journal of surfaces and colloids 2011, 27, 7024-7033.
(91) Huff, T.; Tong, L.; Zhao, Y.; Hansen, M.; Cheng, J.-X.; Wei, A.
Hyperthermic effects of gold nanorods on tumor cells. Nanomedicine 2007, 2, 125-132.
(92) Huang, X.; Jain, P.; El-Sayed, I.; El-Sayed, M. Gold nanoparticles: interesting optical properties and recent applications in cancer diagnostics and therapy.
Nanomedicine 2007, 2, 681-693.
(93) Hu, M.; Novo, C.; Funston, A.; Wang, H.; Staleva, H.; Zou, S.; Mulvaney, P.;
Xia, Y.; Hartland, G. Dark-field microscopy studies of single metal nanoparticles:
understanding the factors that influence the linewidth of the localized surface plasmon resonance. Journal of Materials Chemistry 2008, 18, 1949-1960.
(94) Dreaden, E.; Mwakwari, S.; Austin, L.; Kieffer, M.; Oyelere, A.; El-Sayed, M.
Small molecule-gold nanorod conjugates selectively target and induce macrophage cytotoxicity towards breast cancer cells. Small (Weinheim an der Bergstrasse, Germany)
2012, 8, 2819-2822.
(95) Albanese, A.; Chan, W. Effect of gold nanoparticle aggregation on cell uptake and toxicity. ACS nano 2011, 5, 5478-5489.
(96) Yang, H.-W.; Liu, H.-L.; Li, M.-L.; Hsi, I. W.; Fan, C.-T.; Huang, C.-Y.; Lu, Y.-J.; Hua, M.-Y.; Chou, H.-Y.; Liaw, J.-W.; Ma, C.-C. M.; Wei, K.-C. Magnetic
64
gold-nanorod/ PNIPAAmMA nanoparticles for dual magnetic resonance and photoacoustic imaging and targeted photothermal therapy. Biomaterials 2013, 34, 5651-5660.
(97) Ming, M.; Ya, W.; Jie, Z.; Yongkang, S.; Yu, Z.; Ning, G. Size dependence of specific power absorption of Fe3O4 particles in AC magnetic field. Journal of
Magnetism and Magnetic Materials 2004, 268, 33-39.
(98) Lu, A.-H.; Salabas, E.; Schüth, F. Magnetic nanoparticles: synthesis,
protection, functionalization, and application. Angewandte Chemie (International ed. in English) 2007, 46, 1222-1244.
(99) Lee, J.-H.; Huh, Y.-M.; Jun, Y.-w.; Seo, J.-w.; Jang, J.-t.; Song, H.-T.; Kim, S.; Cho, E.-J.; Yoon, H.-G.; Suh, J.-S.; Cheon, J. Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging. Nature medicine 2007, 13, 95-99.
(100) Key, J.; Aryal, S.; Gentile, F.; Ananta, J.; Zhong, M.; Landis, M.;
Decuzzi, P. Engineering discoidal polymeric nanoconstructs with enhanced magneto-optical properties for tumor imaging. Biomaterials 2013, 34, 5402-5410.
(101) Corot, C.; Robert, P.; Idée, J.-M.; Port, M. Recent advances in iron oxide nanocrystal technology for medical imaging. Advanced drug delivery reviews 2006, 58, 1471-1504.
(102) Chu, M.; Shao, Y.; Peng, J.; Dai, X.; Li, H.; Wu, Q.; Shi, D.
Near-infrared laser light mediated cancer therapy by photothermal effect of Fe3O4 magnetic nanoparticles. Biomaterials 2013, 34, 4078-4088.
(103) Cho, M.; Lee, E.; Son, M.; Lee, J.-H.; Yoo, D.; Kim, J.-w.; Park, S.; Shin, J.-S.; Cheon, J. A magnetic switch for the control of cell death signalling in in vitro and in vivo systems. Nature materials 2012, 11, 1038-1043.
(104) Gupta, A.; Gupta, M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 2005, 26, 3995-4021.
(105) Zhao, Y.; Trewyn, B.; Slowing, I.; Lin, V. Mesoporous silica nanoparticle-based double drug delivery system for glucose-responsive controlled
release of insulin and cyclic AMP. Journal of the American Chemical Society 2009, 131, 8398-8400.
(106) Wang, L.-S.; Wu, L.-C.; Lu, S.-Y.; Chang, L.-L.; Teng, I. T.; Yang, C.-M.; Ho, J.-A. Biofunctionalized phospholipid-capped mesoporous silica nanoshuttles for targeted drug delivery: improved water suspensibility and decreased nonspecific protein binding. ACS nano 2010, 4, 4371-4379.
(107) Lee, J.; Lee, N.; Kim, H.; Kim, J.; Choi, S.; Kim, J.; Kim, T.; Song, I.;
65
Park, S.; Moon, W.; Hyeon, T. Uniform mesoporous dye-doped silica nanoparticles decorated with multiple magnetite nanocrystals for simultaneous enhanced magnetic resonance imaging, fluorescence imaging, and drug delivery. Journal of the American Chemical Society 2010, 132, 552-557.
(108) Hsiung-Lin, T.; Yu-Shen, L.; Hsia-Yu, L.; Yann, H.; Leu-Wei, L.;
Yang-Fang, C.; Chung-Yuan, M. In vitro Studies of Functionalized Mesoporous Silica Nanoparticles for Photodynamic Therapy. Advanced Materials 2009, 21, 172-177.
(109) Shi Kam, N.; Jessop, T.; Wender, P.; Dai, H. Nanotube molecular transporters: internalization of carbon nanotube-protein conjugates into Mammalian cells. Journal of the American Chemical Society 2004, 126, 6850-6851.
(110) Pantarotto, D.; Singh, R.; McCarthy, D.; Erhardt, M.; Briand, J. P.; Prato, M.; Kostarelos, K.; Bianco, A. Functionalized carbon nanotubes for plasmid DNA gene delivery. Angewandte Chemie (International ed. in English) 2004, 43, 5242-5246.
(111) Liu, Z.; Tabakman, S.; Welsher, K.; Dai, H. Carbon nanotubes in biology and medicine: in vitro and in vivo detection, imaging and drug delivery. Nano research
2009, 2, 85-120.
(112) Liu, Z.; Sun, X.; Nakayama-Ratchford, N.; Dai, H. Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery. ACS nano
2007, 1, 50-56.
(113) Foldvari, M.; Bagonluri, M. Carbon nanotubes as functional excipients for nanomedicines: II. Drug delivery and biocompatibility issues. Nanomedicine : nanotechnology, biology, and medicine 2008, 4, 183-200.
(114)
http://www.madsci.org/posts/archives/2006-12/1164999854.Bc.r.html
(Accessed July, 2003)(115) Wang, S.; Luo, J.; Lantrip, D.; Waters, D.; Mathias, C.; Green, M.;
Fuchs, P.; Low, P. Design and synthesis of [111In]DTPA-folate for use as a tumor-targeted radiopharmaceutical. Bioconjugate chemistry 1997, 8, 673-679.
(116) Ross, T.; Honer, M.; Lam, P.; Mindt, T.; Groehn, V.; Schibli, R.;
Schubiger, P.; Ametamey, S. Fluorine-18 click radiosynthesis and preclinical evaluation of a new 18F-labeled folic acid derivative. Bioconjugate chemistry 2008, 19,
2462-2470.
(117) McAlinden, T.; Hynes, J.; Patil, S.; Westerhof, G.; Jansen, G.;
Schornagel, J.; Kerwar, S.; Freisheim, J. Synthesis and biological evaluation of a fluorescent analogue of folic acid. Biochemistry 1991, 30, 5674-5681.
(118) Ho, J.-a.; Hung, C.-H.; Wu, L.-C.; Liao, M.-Y. Folic acid-anchored
66
PEGgylated phospholipid bioconjugate and its application in a liposomal
immunodiagnostic assay for folic acid. Analytical chemistry 2009, 81, 5671-5677.
(119) Gabizon, A.; Horowitz, A.; Goren, D.; Tzemach, D.;
Mandelbaum-Shavit, F.; Qazen, M.; Zalipsky, S. Targeting folate receptor with folate linked to extremities of poly(ethylene glycol)-grafted liposomes: in vitro studies.
Bioconjugate chemistry 1999, 10, 289-298.
(120) Buerkle, L.; Rowan, S. Supramolecular gels formed from
multi-component low molecular weight species. Chemical Society reviews 2012, 41, 6089-6102.
(121) Guiying, L.; Sen, S.; Lei, G.; Songmei, M. Self-assembly of thermo- and pH-responsive poly(acrylic acid)- b -poly( N -isopropylacrylamide) micelles for drug delivery. Journal of Polymer Science Part A: Polymer Chemistry 2008, 46, 5028-5035.
(122) Dufresne, M. H.; Garrec, D.; Sant, V.; Leroux, J. C.; Ranger, M.
Preparation and characterization of water-soluble pH-sensitive nanocarriers for drug delivery. International journal of pharmaceutics 2004, 277, 81-90.
(123) Soo Jin, B.; Ju Myung, S.; Youn Soo, S.; You Han, B.; Sung Wan, K.;
Byeongmoon, J. Thermogelling Poly(caprolactone- b -ethylene glycol- b -caprolactone) Aqueous Solutions. Macromolecules 2005, 38, 5260-5265.
(124) Hwang, M.; Suh, J.; Bae, Y.; Kim, S.; Jeong, B. Caprolactonic poloxamer analog: PEG-PCL-PEG. Biomacromolecules 2005, 6, 885-890.
(125) So Young, K.; Hyun Jeong, K.; Kyung Eun, L.; Sung Sik, H.; Youn Soo, S.; Byeongmoon, J. Reverse Thermal Gelling PEG−PTMC Diblock Copolymer
Aqueous Solution. Macromolecules 2007, 40, 5519-5525.
(126) Jeong, B.; Bae, Y.; Kim, S. Drug release from biodegradable injectable thermosensitive hydrogel of PEG-PLGA-PEG triblock copolymers. Journal of
controlled release : official journal of the Controlled Release Society 2000, 63, 155-163.
(127) Jeong, B.; Bae, Y.; Kim, S. In situ gelation of PEG-PLGA-PEG triblock copolymer aqueous solutions and degradation thereof. Journal of biomedical materials research 2000, 50, 171-177.
(128) Xian Jun, L.; Vu Phuong Nam, N.; Ningyi, K.; Jun, L. Encapsulation of basic fibroblast growth factor in thermogelling copolymers preserves its bioactivity.
Journal of Materials Chemistry 2011, 21, 2246-2254.
(129) Sosnik, A.; Cohn, D. Reverse thermo-responsive poly(ethylene oxide) and poly(propylene oxide) multiblock copolymers. Biomaterials 2005, 26, 349-357.
67
(130) Fleige, E.; Quadir, M.; Haag, R. Stimuli-responsive polymeric
(130) Fleige, E.; Quadir, M.; Haag, R. Stimuli-responsive polymeric