Multifunctional antitumor magnetite/chitosan-l-glutamic acid (core/shell) nanocomposites
- 368 Downloads
The development of anticancer drug delivery systems based on biodegradable nanoparticles has been intended to maximize the localization of chemotherapy agents within tumor interstitium, along with negligible drug distribution into healthy tissues. Interestingly, passive and active drug targeting strategies to cancer have led to improved nanomedicines with great tumor specificity and efficient chemotherapy effect. One of the most promising areas in the formulation of such nanoplatforms is the engineering of magnetically responsive nanoparticles. In this way, we have followed a chemical modification method for the synthesis of magnetite/chitosan-l-glutamic acid (core/shell) nanostructures. These magnetic nanocomposites (average size ≈340 nm) exhibited multifunctional properties based on its capability to load the antitumor drug doxorubicin (along with an adequate sustained release) and its potential for hyperthermia applications. Compared to drug surface adsorption, doxorubicin entrapment into the nanocomposites matrix yielded a higher drug loading and a slower drug release profile. Heating characteristics of the magnetic nanocomposites were investigated in a high-frequency alternating magnetic gradient: a stable maximum temperature of 46 °C was successfully achieved within 40 min. To our knowledge, this is the first time that such kind of stimuli-sensitive nanoformulation with very important properties (i.e., magnetic targeting capabilities, hyperthermia, high drug loading, and little burst drug release) has been formulated for combined antitumor therapy against cancer.
KeywordsBiodegradable nanoparticle Cancer Doxorubicin Hyperthermia Magnetically responsive drug nanocarrier Multifunctional nanoformulation Nanomedicine
Financial support from project PE2008-FQM-3993 (Junta de Andalucía) is acknowledged. D.P. Santos also gratefully acknowledges the financial support of FAPESP (research fellowship: process no. 2007/07914-7).
- Jordan A, Scholz R, Maier-Hauff K, Johannsen M, Wust P, Nadobny J, Schirra H, Schmidt H, Deger S, Loening S, Lanksch W, Felix R (2001) Presentation of a new magnetic field therapy system for the treatment of human solid tumors with magnetic fluid hyperthermia. J Magn Magn Mater 225:118–126. doi: 10.1016/S0304-8853(00)01239-7 CrossRefGoogle Scholar
- Lyklema J (2002) The role of surface conduction in the development of electrokinetics. In: Delgado AV (ed) Interfacial electrokinetics and electrophoresis. Marcel Dekker, New York, pp 87–98Google Scholar
- Lyon RJP (1967) Infrared absorption spectroscopy. In: Zussman J (ed) Physical methods in determinative mineralogy. Academic Press, London/New York, pp 371–399Google Scholar
- Needham D, Anyarambhatla G, Kong G, Dewhirst MW (2000) A new temperature-sensitive liposome for use with mild hyperthermia: characterization and testing in a human tumor xenograft model. Cancer Res 60:1197–1201Google Scholar
- Okon E, Pouliquen D, Okon P, Kovaleva ZV, Stepanova TP, Lavit SG, Kudryavtsev BN, Jallet P (1994) Biodegradation of magnetite dextran nanoparticles in the rat: a histologic and biophysical study. Lab Invest 71:895–903Google Scholar
- Ruiz MA, Gallardo V, Arias JL, Delgado A (2003) Effect of latex and plasticizer concentration on glucocorticoid release from ointments. Pharm Ind 65:454–457Google Scholar
- Sun JB, Duan JH, Dai SL, Ren J, Zhang YD, Tian JS, Li Y (2007) In vitro and in vivo antitumor effects of doxorubicin loaded with bacterial magnetosomes (DBMs) on H22 cells: the magnetic bio-nanoparticles as drug carriers. Cancer Lett 258:109–117. doi: 10.1016/j.canlet.2007.08.018 CrossRefGoogle Scholar
- van Oss CJ (2006) Interfacial forces in aqueous media, 2nd edn. CRC Press, Boca Raton, FLGoogle Scholar