Analytical Science and Technology (분석과학)

The Korean Society of Analytical Sciences (한국분석과학회)
권호 표지
DOI QR코드

DOI QR Code

Antitumor agents bound to silica nanoparticles: potential technology for the remediation of malignant tumors

실리카 나노 입자에 결합된 항종양제: 악성종양 치료를 위한 새로운 치료 방법

  • Received : 2009.09.08
  • Accepted : 2010.12.02
  • Published : 2010.12.25
Download PDF
⟨ Previous Next ⟩

Abstract

Commercially widely used antitumor agents such as hydroxy urea, 6-mercaptopurine monohydrate, cytosine arabinoside, cyclophosphamide monohydrate and uracil were reacted with 3-(triethoxysilyl)propyl isocyanate and the product hydrolyzed to give silica nanoparticles bound antitumor agents ranging from 10 nm to micron-sized aggregates. The silyl isocyanate derivative was also reacted neat with water to give hybrid organicsilicananoparticles containing $-CH_2-CH_2-CH_2-NH-COOH$ or the corresponding decarboxylated propylamine groups depending on solvent and temperature employed. In vitro tests these functionalized silica nanoparticles were effective in the treatment of malignant tumor cells but had little or no effect on normal cells. Malignant human lung, ovarian, melanoma, CNS(Central nervous system) and colon tumor cells were used in this research. The use of silica as a carrier medium in the present research serves as a model material due to its ready functionalization via silation. The proof of concept established by the results suggests that the technique may be applied to other, more biocompatible carrier nanoparticles.

현재 상업적으로 널리 사용 되여 지고 있는 항암제인 hydroxy urea, 6-mercaptopurine monohydrate, cytosine arabinoside, cyclophosphamide monohydrate 그리고 uracil를 3-(triethoxysilyl) propyl isocyanate 와 반응시켜 항암제가 붙어있는 3-(triethoxysilyl)propyl amide (compound I)을 합성한후 물과 가수분해 반응시켜 항암제가 결합된 silica 나노입자(10 nm~micronparticles)를 만들 수있었다. Silyl isocyanate 유도체들은 물과 반응하여 유기물질-silica 나노입자가 포함된 $-CH_2-CH_2-CH_2-NH-COOH$ 그룹이나 혹은 온도와 용매등 반응조건에 따라서 decarboxylated 된 propylamine 그룹이 생성되었다. 생체외 시험에서 항암제가 결합된 silica 나노입자는 종양 세포 제거에 효과적이고 정상세포에 거의 영향을 미치지 않는 것으로 나타났다. 그리고 악성 종양인 폐, 난소, 악성 흑색종, 중추신경계(CNS)와 결장 종양 세포가 이 연구에 사용되었다. 현재의 연구에서 전달매체 로서 silica는 silation 반응으로 손쉽게 나노입자를 얻을 수 있으므로 본 연구에 쉽게 이용 할 수 있다. 결과로부터 이 기술은 보다 부작용이 적은 생체 의약품에 적합한 carrier nanoparticles에 적용 될 수 있을 것으로 판단된다.

Keywords

References

  1. Higashi, Sohei (Nanocarrier Co., Ltd., Japan). Farumashia 2002, 38(4), 345-346 (Japan).
  2. Xu, Jingya (Fannin Bioscience, Inc., USA) PCT Int. Appl. WO 00 61,788 (C1. C12Q), 19 Oct 2000, US Appl. 291,234,13 Apr 1999; 65pp. (Eng).
  3. Rihova, B. (Polymer Materials Research Group, University of Gent, 9000 Ghent, Belg.). Proc. Int. Symp. Controlled Release Bioact. Mater. 1999, $26^{th}$, 627-628 (Eng).
  4. Deggi, Neil P; Soon-Shiong, Patrick; Magdassi, Shlomo; Sahadevan, David D. (Vivorx Pharmaceuticals, Int., USA) PCT Int. Appl. WO 99 00,113 (C1. A61K9/ 22), 7 Jan 1999, US Appl, 926,155,9 Sep 1997; 175pp. (Eng).
  5. Lavi, Sara; Satchi-Fainaro, Ronit (Ramot-University Authority for Applied Research and Industrial Development Ltd., Israel) PCT Int. Appl. WO 02 07,670 (C1. A61K), 31 Jan 2002, US Appl. 668,714, 22 Sep 2000; 66pp. (Eng).
  6. Lavi, Sara; Satchi-Fainaro, Ronit (Ramot-University Authority for Applied Research and Industrial Development Ltd., Israel) PCT Int. Appl. WO 02 07,671 (C1. A61K), 31 Jan 2002, US Appl. 668,713, 22 Sep 2000; 73pp. (Eng).
  7. Fotinos, Spiros; O'Halloran, David; Zolotarsky, Yelena (Lavipharm Laboratories Inc., USA) PCT Int. Appl. WO 02 54,997 (C1. A61F13/00), 18 Jul 2002, US Appl. PV260, 587, 9 Jan 2001; 20pp. (Eng).
  8. Liggins, Richard; Murphy, Larry; Guan, Dechi (Angioteth Pharmaceuticals Inc., Can.) PCT Int. Appl. WO 02 72,150 (C1. A61K47/48), 19 sep 2002, US Appl. PV337,935, 7 N
  9. Nizard, Philippe; Gross, David-Alexandre; Chenal, Alexandre; Beaumelle, Bruno; Kosmatopoulos, Konstadinos; Gillet, Daniel (Deparetment d'Ingenierie et d'Etudes des Proteines, CEA-Saclay, 91191 Gif-sur-Yvette, FR.). Journal de la Societe de Biologie 2001, 195(3), 229-234(Fr). https://doi.org/10.1051/jbio/2001195030229
  10. Unger, Gretchen M. (Genesegues, Inc., USA) PCT Int. Appl. WO 01 64,164 (C1. A61K), 7 Sep 2001, US Appl. PV185,282, 28 Fed 2000; 70 pp. (Eng).
  11. Burman, Anand C.; Mukherjee, Rama; Khattar, Dhiraj; Kumar, Mukesh; Bala, Honey; Shrivastava, Rajiv Kumar (Dabur Research Foundation, India) U.S. US 6,365,191 (C1. 424-489; A61K9/14), 2 Apr 2002, IN Appl. 2000/DE641, 11 Jul 2000; 8 pp., Cont.-in-part of U.S. Ser. No. 401,927. (Eng).
  12. Maitra, Amarnath; Sahoo, Sanjeeb Kumar, Ghosh, Prasanta Kuma; Burman, Anand C.; Mukherjee, Rama; Khattar, Dhiraj; Kumar, Mukesh; Paul, Soumendu (Dabur Research Foundation; Delhi University, India) U.S. US 6,322,817 (C1. 424-489; A61K47/30), 27 Nov 2001, IN Appl. 1999/DE263, 17 Feb 1999; 10 pp. (Eng).
  13. Fukumori, Yoshinobu; Ichikawa, Hideki; Tokumitsu, Hiroyuki; Shikata, Futoshi; Miyamoto, Masahito; Watanabe, Testuya (Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University, Kove, Japan 651-2180), Int. Conf. Process. Mater. Prop. Proc., 2nd 2000, 453-458 (Eng).
  14. Da Silverira, Monza; Ponchel, Gilles; Duchene, Dominique; Couvreur, Patrick; Puisieux, Francis (Bioalliance Pharma (S.A.); Monza Da Silverira, Airton, Fr.) PCT Int. Appl. WO 99 43,359 (C1. A61K47/48), 2 Sep 1999, FR Appl. 1998/2,429, 27 Feb 1998; 56 pp. (Fr).
  15. Balland, Olivier; Saison-Behmoaras, Tula; Garestier, Therese; Helene, Claude (Laboratorie de Biophysique, Museum National Histoire Naturelle, 75231 Paris, Fr.). NATO ASI Ser., Ser. A 1996. 290 (Targeting Drugs 5), 131-142 (Eng).
  16. Jain, S; Jain, N. K. (Department of Pharmaceutical Sciences, DR. H. S. Gour University, Sagar, 470003 India). Proc. Int. Symp. Controlled Release Bioact. mater. 1997, 24th, 857-858 (Eng).
  17. R. Partch; E Powell; Y-H Lee; M. Varshney; S. Kim; N. Barnard; D. Shah; D.Dennis; T. Morey. 2003 Kluwer Academic publishers, Y, G, Gogotsi and I. V. Uvarova (eds.), 27-40.

Cited by

  1. Effect of functional group on activity and stability of lipase immobilized on silica-coated magnetite nanoparticles with different functional group vol.29, pp.3, 2016, https://doi.org/10.5806/AST.2016.29.3.105