Chitosan nanoparticles for combined drug delivery and magnetic hyperthermia: From preparation to in vitro studies.

Chitosan nanoparticles (CSNPs) ionically crosslinked with tripolyphosphate salts (TPP) were employed as nanocarriers in combined drug delivery and magnetic hyperthermia (MH) therapy. To that aim, three different ferrofluid concentrations and a constant 5-fluorouracil (5-FU) concentration were efficiently encapsulated to yield magnetic CSNPs with core-shell morphology. In vitro experiments using normal cells, fibroblasts (FHB) and cancer cells, human glioblastoma A-172, showed that CSNPs presented a dose-dependent cytotoxicity and that they were successfully uptaken into both cell lines. The application of a MH treatment in A-172 cells resulted in a cell viability of 67-75% whereas no significant reduction of cell viability was observed for FHB. However, the A-172 cells showed re-growth populations 4h after the application of the MH treatment when CSNPs were loaded only with ferrofluid. Finally, a combined effect of MH and 5-FU release was observed with the application of a second MH treatment for CSNPs exhibiting a lower amount of released 5-FU. This result demonstrates the potential of CSNPs for the improvement of MH therapies.

[1]  F. Goycoolea,et al.  Chapter 25 – Chitin and Chitosan: Major Sources, Properties and Applications , 2008 .

[2]  Hyperthermia HeLa Cell Treatment with Silica-Coated Manganese Oxide Nanoparticles , 2009, 0907.3278.

[3]  M. Fernández-Gutiérrez,et al.  Magnetic core-shell chitosan nanoparticles: rheological characterization and hyperthermia application. , 2014, Carbohydrate polymers.

[4]  M. V. Lozano,et al.  Highly efficient system to deliver taxanes into tumor cells: docetaxel-loaded chitosan oligomer colloidal carriers. , 2008, Biomacromolecules.

[5]  Hua Yue,et al.  Codelivery of mTERT siRNA and paclitaxel by chitosan-based nanoparticles promoted synergistic tumor suppression. , 2013, Biomaterials.

[6]  Federica Chiellini,et al.  Chitosan—A versatile semi-synthetic polymer in biomedical applications , 2011 .

[7]  Peter Fredericks,et al.  Interactions between alginate and chitosan biopolymers characterized using FTIR and XPS. , 2007, Biomacromolecules.

[8]  Jianxiu Wang,et al.  Theranostic magnetoliposomes coated by carboxymethyl dextran with controlled release by low-frequency alternating magnetic field. , 2015, Carbohydrate polymers.

[9]  F. Soleymani,et al.  Magnetic/pH-responsive beads based on caboxymethyl chitosan and κ-carrageenan and controlled drug release. , 2015, Carbohydrate polymers.

[10]  P. Mutlu,et al.  Synthesis of Doxorubicin loaded magnetic chitosan nanoparticles for pH responsive targeted drug delivery. , 2014, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[11]  M. Ibarra,et al.  Controlled Cell Death by Magnetic Hyperthermia: Effects of Exposure Time, Field Amplitude, and Nanoparticle Concentration , 2012, Pharmaceutical Research.

[12]  Dong-lin Zhao,et al.  Preparation and inductive heating property of Fe3O4–chitosan composite nanoparticles in an AC magnetic field for localized hyperthermia , 2009 .

[13]  P. Wust,et al.  Magnetic fluid hyperthermia (MFH): Cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles , 1999 .

[14]  N. Batistela,et al.  Synthesis and characterization of the iron oxide magnetic particles coated with chitosan biopolymer , 2008 .

[15]  P. Chu,et al.  Hollow chitosan e silica nanospheres as pH-sensitive targeted delivery carriers in breast cancer therapy , 2011 .

[16]  N. Thanh,et al.  Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer. , 2014, Nanoscale.

[17]  J. San Román,et al.  Effect of the molecular architecture on the thermosensitive properties of chitosan-g-poly(N-vinylcaprolactam). , 2015, Carbohydrate polymers.

[18]  R. Muzzarelli,et al.  Chitosan chemistry : Relevance to the biomedical sciences , 2005 .

[19]  R. Zeng,et al.  Synthesis, Characterization of Biomimetic Phosphorylcholine-Bound Chitosan Derivative and In Vitro Drug Release of Their Nanoparticles , 2013 .

[20]  S. Elmore.  Apoptosis: A Review of Programmed Cell Death , 2007, Toxicologic pathology.

[21]  O. Fatibello‐Filho,et al.  Biosensor based on laccase immobilized on microspheres of chitosan crosslinked with tripolyphosphate , 2008 .

[22]  C. Marquina,et al.  Magnetic Hyperthermia With Fe$_{3}$O $_{4}$ Nanoparticles: The Influence of Particle Size on Energy Absorption , 2008, IEEE transactions on magnetics.

[23]  Qiqing Zhang,et al.  Methotrexate-loaded PEGylated chitosan nanoparticles: synthesis, characterization, and in vitro and in vivo antitumoral activity. , 2014, Molecular pharmaceutics.

[24]  Maria Jose Alonso,et al.  Chitosan-based nanostructures: a delivery platform for ocular therapeutics. , 2010, Advanced drug delivery reviews.

[25]  D. Bikiaris,et al.  Chitosan nanoparticles loaded with dorzolamide and pramipexole , 2008 .

[26]  Nengqin Jia,et al.  Chitosan-coated magnetic nanoparticles as carriers of 5-fluorouracil: preparation, characterization and cytotoxicity studies. , 2009, Colloids and surfaces. B, Biointerfaces.

[27]  C. Kumar,et al.  Magnetic nanomaterials for hyperthermia-based therapy and controlled drug delivery. , 2011, Advanced drug delivery reviews.

[28]  C. Mijangos,et al.  Use of alginate, chitosan and cellulose nanocrystals as emulsion stabilizers in the synthesis of biodegradable polymeric nanoparticles. , 2015, Journal of colloid and interface science.

[29]  M. Rinaudo,et al.  Chitin and chitosan: Properties and applications , 2006 .

[30]  P. Wust,et al.  The cellular and molecular basis of hyperthermia. , 2002, Critical reviews in oncology/hematology.

[31]  O. Smidsrod,et al.  Determination of the degree of N-acetylation and the distribution of N-acetyl groups in partially N-deacetylated chitins (chitosans) by high-field n.m.r. spectroscopy. , 1991, Carbohydrate research.

[32]  K. Neoh,et al.  Polymeric nanoparticles with encapsulated superparamagnetic iron oxide and conjugated cisplatin for potential bladder cancer therapy. , 2012, Biomacromolecules.

[33]  P. Johnston,et al.  5-Fluorouracil: mechanisms of action and clinical strategies , 2003, Nature Reviews Cancer.

[34]  A. Tres,et al.  Induced cell toxicity originates dendritic cell death following magnetic hyperthermia treatment , 2013, Cell Death and Disease.

[35]  Carlos Rinaldi,et al.  EGFR-targeted magnetic nanoparticle heaters kill cancer cells without a perceptible temperature rise. , 2011, ACS nano.

[36]  Yu-Che Huang,et al.  Microfluidic emulsification and sorting assisted preparation of monodisperse chitosan microparticles. , 2009, Lab on a chip.

[37]  Ajay Kumar Gupta,et al.  Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. , 2005, Biomaterials.

[38]  Morteza Mahmoudi,et al.  Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles. , 2011, Advances in colloid and interface science.

[39]  J. Majoral,et al.  Advances in combination therapies based on nanoparticles for efficacious cancer treatment: an analytical report. , 2015, Biomacromolecules.

[40]  Ajay Kumar Gupta,et al.  Cytotoxicity suppression and cellular uptake enhancement of surface modified magnetic nanoparticles. , 2005, Biomaterials.