Abstract
Sustaining the release of therapeutic nanoparticles in a cell-, tissue-, or disease-specific manner is a potentially powerful technology. A new drug carrier-dialdehyde starch nanoparticle (DASNP) that can sustain the loading and release of 5-fluorouracil (5-Fu) antitumor drug is reported in this study. IR spectrophotometer and 1H NMR confirmed the formation of aldehyde groups, and scan electron microscope determinations showed that the dialdehyde starch nanoparticles obtained had an average diameter of 90 nm. 5-Fu, the model drug, was conjugated into nanoparticles by aldehyde groups. These 5-Fu-binding nanoparticles significantly enhanced breast cancer cell (MCF-7) inhibition in vitro compared with free 5-Fu. After subcutaneous 0 injection in the breast tumor-loaded rats, 5-Fu-DASNP exhibited remarkable tumor-inhibitory efficacy determined by measuring tumor weight in vivo. The tumor inhibition of 5-Fu-DASNP was 61%±6%, whereas that of free 5-Fu was only 42%±4%. Bcl-2/Bax immunohistochemistry studies indicated that 5-Fu-DASNP remarkably induced tumor tissue necrosis. These results demonstrated that the DASNP prepared in this work is a potentially effective drug carrier.
Article PDF
Similar content being viewed by others
References
He X, Shen B, Liu X. Production and applications on dialdehyde starch (in Chinese). Chin J Bioprocess Eng, 2004, 2: 1–4
Wongsagona R, Shobsngobb S, Varavinita S. Preparation and physicochemical properties of dialdehyde tapioca starch. Starch Starke, 2005, 57: 166–172
Para A, Karolczyk-Kostuch S. Metal complexes of starch dialdehyde dithiosemicarbazone. Carbohydr Polym, 2002, 50: 151–158
Tang R, Du Y, Fan L. Dialdehyde starch-crosslinked chitosan films and their antimicrobial effects. J Polym Sci Pt B-Polym Phys, 2003, 41: 993–997
Wang H, Wei R, Shen H, et al. Study on flexible immobilized papain with dialdehyde Starch (in Chinese). Chin J Bioprocess Eng, 2004, 2: 25–29
Onishi H, Nagai T. Characterization and evaluation of dialdehyde starch as an erodible medical polymer and a drug carrier. Int J Pharm, 1986, 30: 133–141
Langmaier F, Mokrejs P. Hydrogels of collagen hydrolysate cross-linked with dialdehyde starch. J Therm Anal Calorim, 2009, 98: 807–812
Song Y, Tu J, Zheng Q. A comparison study of wheat gluten composites filled with dialdehyde starch and native starch. J Polym Environ, 2010, 18: 260–265
Zhang S, Wang X, Zhang Y. Preparation of a new dialdehyde starch derivative and investigation of its thermoplastic properties. J Polym Res, 2010, 17: 439–446
Para A, Karolczyk-Kostuch S, Fiedorowicz M. Dihydrazone of dialdehyde starch and its metal complexes. Carbohydr Polym, 2004, 56: 187–193
Para A. Complexation of metal ions with dioxime of dialdehyde starch. Carbohydr Polym, 2004, 57: 277–283
Onishi H, Nagai T. Characterization and evaluation of dialdehyde starch as an erodible medical polymer and a drug carrier. Int J Pharm, 1986, 30: 133–141
Chen H G, Liu L W, Lü S, et al. Immobilization of aspergillus niger xylanase on chitosan using dialdehyde starch as a coupling agent. Appl Biochem Biotechnol, 2010, 162: 24–32
Yu D M, Xiao S Y, Tong C Y, et al. Dialdehyde starch nanoparticles: Preparation and application in drug carrier. Chin Sci Bull, 2007, 52: 2913–2918
Benbowa J W, Aubrechtb J, Banker M J, et al. Predicting safety toleration of pharmaceutical chemical leads: Cytotoxicity correlations to exploratory toxicity studies. Toxicol Lett, 2010, 197: 175–182
Prakasa Babu P, Yoshida Y, Su M, et al. Immunohistochemical expression of Bcl-2, Bax and cytochrome following focal cerebral ischemia and effect of hypothermia in rat. Neurosci Lett, 2000, 291: 196–200
Hanafy S M, Shehata O H, Farahat N M. Expression of apoptotic markers Bcl-2 and Bax in chronic hepatitis C virus patients. Clin Biochem, 2010, 43: 1112–1117
Azevedo A M, Martins V C, Prazeres D M, et al. Horseradish peroxidase: A valuable tool in biotechnology. Biotechnol Annu Rev, 2003, 9: 199–247
Smith A A. Specifc staining of tissue components with metal-hematoxylin complexes. Micron, 2002, 33: 95–103
Veelaert S, Wit D D, Gotlibt K F, et al. Chemical and physical transitions of periodate oxidized potato starch in water. Carbohydr Polym, 1997, 33: 153–162
Para A, Karolczyk-Kostuch S, Hajdon T, et al. Dialdehyde starch of low degree of oxidation and its derivatives. Pol J Food Nutr Sci, 2000, 50: 7–12
Cao S, Frank C, Shirasaka T, et al. 5-Fluorouracil prodrug: Role of anabolic and catabolic pathway modulation in therapy of colorectal cancer. Clin Cancer Res, 1995, 1: 839–845
Daumar P, Decombat C, Chezal J M, et al. Design, synthesis and in vitro drug release investigation of new potential 5-Fu prodrugs. Eur J Med Chem, 2011, 46: 2867–2879
Fournier E, Passirani C, Colin N. Development of novel 5-Fu-loaded poly (methylllidene malonate)-based microspheres for the treatment of brain cancers. Eur J Pharm Biopharm, 2004, 57: 189–197
Lamprecht A, Yamamoto H, Takeuchi H, et al. Microsphere design for the colonic delivery of 5-fluorouracil. J Control Release, 2003, 90: 313–322
Marija G D, Emilija F K, Katerina G, et al. 5-Fluorouracil in topical liposome gels for anticancer treatment-Formulation and evaluation. Acta Pharm, 2003, 53: 241–250
Para A, Ropek D. Starch dialdehyde derivatives as novel complexions protecting entomopathogenic nematodes from heavy metals. Chemiai Inz Ekol, 2000, 7: 1213–1220
Han W, Chen Y, Liu W. Effects of chemotherapeutic drugs on proliferation of tongue carcinoma cells (in Chinese). J Jilin Univ, 2006, 32: 672–674
Author information
Authors and Affiliations
Corresponding authors
Additional information
This article is published with open access at Springerlink.com
Rights and permissions
This article is published under an open access license. Please check the 'Copyright Information' section either on this page or in the PDF for details of this license and what re-use is permitted. If your intended use exceeds what is permitted by the license or if you are unable to locate the licence and re-use information, please contact the Rights and Permissions team.
About this article
Cite this article
Xiao, S., Liu, X., Tong, C. et al. Dialdehyde starch nanoparticles as antitumor drug delivery system: An in vitro, in vivo, and immunohistological evaluation. Chin. Sci. Bull. 57, 3226–3232 (2012). https://doi.org/10.1007/s11434-012-5342-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11434-012-5342-5