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Antitumoural Nanocomposites

#A-1563


Formation of Metal Oxide Nanocomposites with Anticancer Activity from the Salicylidene Amino Acids Family

Tech Area / Field

  • CHE-SYN/Basic and Synthetic Chemistry/Chemistry
  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • CHE-POL/Polymer Chemistry/Chemistry
  • MAT-COM/Composites/Materials
  • MAT-SYN/Materials Synthesis and Processing/Materials

Status
8 Project completed

Registration date
03.09.2007

Completion date
28.12.2011

Senior Project Manager
Mitina L M

Leading Institute
State Engineering University of Armenia, Armenia, Yerevan

Supporting institutes

  • Scientific Technological Centre of Organic and Pharmaceutical Chemistry SNPO / Institute of Fine Organic Chemistry, Armenia, Yerevan

Collaborators

  • University of Oxford / Chemical Research Laboratory, UK, Oxford\nUniversity of Central Lancashire, UK, Preston\nUniversity of Dublin / Trinity College Dublin, Ireland, Dublin\nQueen Mary, University of London / Interdisciplinary Centre in Biomedical Materials, UK, London\nUniversity of Cambridge / Engineering Department, UK, Cambridge

Project summary

At present, various hybrid techniques are intensively developed which use the methods and tools of molecular biology, medicine and nanotechnology aimed at the surface modification of biologically active materials for the formation of nanocomposite structures. It is known that biologically active materials formed by the deposition of metal oxide nanostructures on the surface of organic, polymeric systems reveal a remarkable ability to suppress and destruct - at their introduction in organisms - pathogenic biological flora and prevent the "fastening" of viruses and bacteria to cell walls, increase antibacterial and virus-induced immunity. Nanotechnologies are especially important for the creation of anticancer drugs. The majority of modern anticancer drugs are characterized - alongside with high activity – by expressed toxicity. Their application in therapeutic doses is accompanied, as a rule, by various toxicity symptoms that frequently result in the cessation of the further course of treatment. This feature of anticancer therapy testifies the expediency of the development of new approaches to the creation of anticancer compounds directed to the maintenance andor increase of anticancer activity using relatively small doses of the selective action materials. The results obtained during preliminary investigations of chemical gas-phase deposition of ZnO thin films on copper ethyl ether salycylidene DL-tyrosine complex, biologically active compound characterized by expressed antioxidant and anticancer properties, have shown an increase in anticancer activity of the composite (ZnO-chelate) together with the decrease in toxicity in comparison with the initial compound. Laboratory samples were tested on sarcoma 45 vaccinated rats ith the initial compound. Laboratory samples were tested on sarcoma 45 vaccinated rats in the Institute of Fine Organic Chemistry of the National Academy of Sciences of the Republic of Armenia (IFOC NAS RA).

Zinc oxide is one of the unique materials with antioxidant, antimicrobial activity, supporting the immune system of organisms. Basic amino acids in organisms are binding substances for metal oxides, particularly, for ZnO, and Zn complexes control - indirectly, through the biosynthesis of metalloproteins which perform the role of electron donors for glutation-peroxidase systems - the cell content of peroxides. Semiconductor ZnO films are distinguished for their specific optical and electrical properties in view of opportunity to change the films specific resistance over very wide limits:

3·10-4 - 2·107 ohm·cm. From the above reasoning it is clear that ZnO is one of promising materials for modification of biologically active surfaces. There is a series of publications on modification of material surfaces (polymers, cellulose fibers, paper) by ZnO nanoparticles, however, there are no works on deposition of biologically active compounds (antitumor activity) on thermolabile surfaces at relatively low temperatures. The development of materials capable - due to their structural and electrophysical parameters - to prevent the development of tumour cells, accelerate their destruction as well as maintain or decrease the compounds toxicity is now an actual problem.

The offered Project assumes synthesis of new antitumoral salicylidene amino acids and their Cu (II) chelates containing in their molecules amino acid residues of DL-tyrosine, DL-β-phenyl-α-alanine, ω-aminocaproic acid, DL-tryptophan, and the development of their surface modification method by deposition of zinc oxide nanoparticles to obtain low toxic antitumoural ZnO-ligand and ZnO-chelate nanocompounds. The Project assumes a new approach to the surface modification of biologically active compounds having antitumor activity aimed at the creation of nanocomposites together with a detailed investigation of some opportunities using the following promising modern methods for the formation of metal oxide nanosized structures: ILGAR method for the formation of films and coverings of biologically active compounds of salycylidene amino acids type, and DC magnetron deposition of non-doped and Ag-doped thin nanosized ZnO films for these compounds’ surface modification. These methods are stand out by their wide possibilities for controllable synthesis of metal oxide nanocomposites, low deposition temperature and simple techniques of doping, layer-by-layer deposition of nanofilms, etc., that allow growing of nanocomposites with predetermined structure and physical parameters. An important feature of the proposed approach to surface modification of antitumoural compounds is increase of antitumoral activity simultaneously with the decrease of toxicity depending on the average size and distribution of ZnO nanoparticles in nanocomposites at T 100oC, when there are no undesirable secondary transformations.

Within the framework of the Project it is supposed to solve the following five global problems:

  1. Determination of optimum kinetic and dynamic parameters of the process of nanocomposition formation by the improved method of DC-magnetron surface modification of ethyl ether salicylidene DL-tyrosine, salicylidene DL-β-phenyl-α-alanine and their Cu (II) chelates by ZnO.
  2. Search of the nanocomposition obtaining conditions. Dependence of antitumoural activity on the structure, electrical and physical parameters of metal-oxide nanocompositions.
  3. Obtaining of nanocompositions by controlling the kinetic and dynamic parameters of the process of improved DC-magnetron surface modification of salicylidene ω-aminocaproic acid, salicylidene DL-tryptophan and Cu(II) chelates by ZnO.
  4. Formation of metal-oxide nanocomposition materials with antitumoral activity in a water-soluble polymeric matrix for durable action.
  5. Development of a technology for producing metal oxide nanocompositions.

To obtain metal oxide nanocompositions of salicylidene anino acid family: DL-tyrosine, DL-β-phenyl-α-alanine, ω-aminocaproic acid, DL-tryptophan and their Cu (II) chelates, the following scientific and technical approaches will be used:
  1. Physical methods of nanocomposites deposition (ILGAR, DC magnetron deposition).
  2. Chemical, spectral and structural methods of analysis for the study of structures of the above mentioned compound families.
  3. X-ray diffraction analysis, electron microscopy, microanalysis, ellipsometry, electron-tunnel and capacitance-tunnel spectroscopy for the study of nanocomposites.
  4. Choice of optimum parameters of physical deposition processes, size and density on nanocomposites for the simulation of their synthesis methods.
  5. Screening of antitumor activity on inoculated tumour strains and toxicity, histological, histochemical, morphometric investigations of various organs of the synthesized compounds of salicylidene amino acids family and nanocompositions.
  6. Mathematical processing of experimental data on the nanocomposite formation mechanism.
  7. Use of optimum kinetic and dynamic parameters (T, P, V) of metal oxide nanocomposites formation process as well as structural and physical characteristics of target and substrate materials for the simulation of methods for metal oxide nanocomposites systems growth.

As a result of research and technological development it is expected to obtain the following results:
  • Determination of optimum kinetic and dynamic parameters for the formation of metal-oxide nanocompositions. Controlling of nanoparticle size and distribution in nanocompositions as well as target properties of nanocompositions on the basis of the obtained kinetic and dynamic properties of the metal-oxide nanocomposite system formation process.
  • Development of a technology for obtaining metal-oxide nanocompositions by the example of: ethyl ether salycilidene DL-tyrosine, salicylidene DL-β-phenyl-α-alanine, salicylidene ω-aminocaproic acid, salicylidene DL-tryptophan and their Cu- (II) chelates.
  • Obtaining of nanocompositions with antitumoural activity, low toxicity and predetermined electrophysical characteristics.
  • Modification of the developed method for obtaining various metal-oxide nanocomposition systems.

Fulfillment of the planned tasks will enable to:
  • develop a process of obtaining various metal-oxide nanocomposition systems based on the proposed salicylidene amino acids: DL-tyrosine, DL-β-phenyl-α-alanine, ω-aminocaproic acid, DL-tryptophan and their Сu (II) chelates coated with deposited nanosized ZnO structures on their surfaces ;
  • create a high efficient non-polluting, cost effective and technologically reproducible process of obtaining metal-oxide nanocompositions of salicylidene amino acids with antitumoural activity, low toxicity;
  • involve in the work program highly qualified specialists, scientists earlier engaged in the development and production of weapon;
  • participation of Armenian scientists in joint scientific investigations, workshops with collaborators, international conferences will assist their integration in international scientific community.

It is assumed to organize – on the basis of scientific investigations and technological developments – a flow diagram for the modeling of biologically active nanocomposite systems and marketing research in the field of medicine and electronics aimed at creation of marketing outlets.


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