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Investigation on Medical Diagnotic and Therapeutic Applications of Prussian Blue Nano-materials

Author: FuGuangLei
Tutor: DaiZhiFei
School: Harbin Institute of Technology
Course: Biomedical Engineering
Keywords: Prussian blue Nano-materials Blood glucose biosensor Photothermaltherapy of cancers Theranostic
CLC: R318.08
Type: PhD thesis
Year: 2013
Downloads: 3
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Abstract

Biomedical diagnosis and therapy are of vital importance for human health.Currently, with the rapid development of science and technology, subject crossinghas been a tendency. Among these subjects, the application of nano-materials inmedical diagnosis and therapy has attracted particular attention. Due to their uni quebiomedical advantages, nano-materials have the potential to address biomedicalproblems of traditional medical methods, guiding new revolution of moderndiagnostic and therapeutic methods. Exploration of novel biomedical functions oftraditional nano-materials as well as the development of novel multifunctionalnano-materials with biomedical applications is promoting a new round of researchinterest. However, the bio-safety of most current nano-materials in vivo isunapproved because most relative investigations are only confined in vitro inaddition to their high price and hard preparation procedure, which greatly limitstheir further development.Prussian blue is a kind of ancient dye with simple preparation and low price.Most importantly, as a typical reserve medicine in hospital, PB is a kind of drug inclinic. The clinical experiences of Prussian blue have demonstrated the reliablebio-safety and metabolism in vivo. Due to these advantages, the biomedical problemof unapproved bio-safety of most other nano-materials could be potentially resolvedonce PB could be further applied to medical diagnosis and therapy. The research andapplication value of PB is considerable.Aiming at the exploration of novel biomedical functions of PB, this studyfocused on PB-based medical diagnosis and therapy. With respect to medicaldiagnosis, biosensor is a type of very cutting-edge medical diagnostic method. Incomparison with traditional diagnostic methods, biosensors are advantageous fortheir point-of-care diagnosis. In this work, blood glucose electrochemical biosensorwas selected as the typical diagnostic model for research. Combining the synergisticbiosensing advantages of PB deposited multiwall carbon nanotubes (MWNTs)hybrids and3-isocyanatopropyltriethoxysilane-based SiO2sol-gel, a novel glucosebiosensor was fabricated based on PB-MWNTs-chitosan-SiO2sol-gel biosensitivemembrane. It was found that the biosensitive membrane possessed both highenzyme immobilization efficiency and good electrochemical properties. Base on thehigh efficient catalysis of PB in the membrane to enzymatically produced H2O2, thebiosensor showed good response to glucose with sensitivity and detection limit of15.2μA/(cm2·mmol/L) and7.5×10-6mol/L, respectively. Compared with the controlbiosensor and relative literatures, the stability, sensitivity and selectivity of the biosensor were superior. In order to further improve the biosensing performance, PBdeposited MWNTs hybrids were employed as the backbone for assembly of enzyme.Another novel glucose biosensor was then fabricated based on the electrostaticself-assembly in combination with in situ photo-cross-liking for enzymeimmobilization on PB deposited MWNTs backbone. Attributed to goodelectrochemical properties of the backbone and high enzyme immobilizationefficiency, the biosensor exhibited greatly improved sensitivity of77.9μA/(cm2·mmol/L), which was obviously higher than that of the control biosensorand literatures. Meanwhile, the biosensing stability was also greatly promoted.Furthermore, the blood glucose detection results in real serum samples using thebiosensor corresponded well with that obtained in the hospital using the traditionalanalytical method, demonstrating reliable ability of the biosensor for practicalapplications. As the typical research model of biosensors, the above blood glucosebiosensors could establish a promising platform for the fabrication of otherbiosensors for medical diagnosis.With respect to medical therapy, cancers have been one of the most significantmedical challenges that human has to be confronted. Hence, in this work,investigation on cancer therapy based on PB nano-materials was further performed.Relying on the application of photothermal agent, photothermal therapy is apreferable therapeutic approach for cancers with low invasiveness and highefficiency. Herein, PB nano-materials were explored for the first time as a newgeneration of near-infrared laser-driven photothermal ablation agents for cancertherapy alternative to traditional agents. PB cubic nanoparticles (PB NPs) withdiameter of40nm with good dispersibility and stability were synthesized. Theas-prepared nanoparticles showed high molar extinction coefficient of109/(cm·mol/L) in the near-infrared region from400to900nm. Moreover, thenanoparticles could convert the absorbed near-infrared light into heat with goodphotothermal conversion efficiency and high photothermal stability in comparisonwith traditional Au nanorods. The cytotoxicity test in vitro exhibited that these PBNPs with low concentration of only16ppm could result in90%cell death throughtheir photothermal effect, holding great potential as a new generation ofphotothermal ablation agent for cancers. To further realize the theranosticapplications of PB-based nano-materials, superparamagnetic Fe3O4nanoparticleswere used as the core for the growth of PB nanoshell with5nm on their surfaces.Due to the unique core-shell structure, the core-shell nanoparticles showedconsiderable photothermal effect in the near-infrared region, and showedorientational movement in magnetic field of a certain intensity. The nanoparticlescould obviously improve the photothermal ablation efficiency of HeLa cells in vitrothrough their magnetic targeted photothermal effect. In addition, the nanoparticles exhibited considerable T2-weighted magnetic resonance imaging performance withT2relaxivity value of58.9/(s·mmol/L). Therefore, the nanoparticles weremultifunctional theranostic nano-agents for magnetic resonance imaging andmagnetic targeted photothermal therapy, which possessed the superiority oftheranostic nano-materials in cancer therapy.Due to the reliable biosafety of PB in vivo, low price and simple preparation,the PB-based blood glucose biosensor model, cancer photothermal ablation agentand multifunctional theranostic nano-agents developed in this work have thepotential to play an important role in point-of-care diagnosis and cancer therapy. Inaddition, with limitless research and application prospect, they have the potential toaddress important biomedical problems of unapproved bio-safety, expensive priceand hard preparation of most other nano-materials. PB nano-materials would be akind of materials with much higher safety and efficiency for medical diagnosis andtherapy, hence promoting the development of nano-materials-based medicaldiagnosis and therapy.

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