The proposal deals with the development of simple synthetic procedure for fabricating cation deficient copper (1) sulfides, Cu2-xS nanorods of varying aspect ratio and the encapsulation in folic acid conjugated heparin to form a bio-conjugate, HF-CuS . This bio-conjugate will have the capabilities to ?seek and attach itself to tumor cells due to the overexpression of folate receptors in such cells. The transport ability of such matrix in physiological fluid will also be enhanced due to the solubility of the heparin, it ability to coat the surface of copper sulfide as a non-cytotoxic, biodegradable polysaccharide. The Cu2-xS should be able to thermally ablate cancer cells when exposed to near infra-red laser light (NIR) of desired wavelength. The NIR laser is less absorbed by biological tissues with typical tissue penetration depth approaching several centimeters for 980 nm light. The work will be accomplished in three steps: 1. The fabrication of Cu2-xS nanorods with various aspect ratios, will be accomplished using a combination of 1-DDT (1 dodecane thiol) and t-DDT (tert-dodecane thiol) as the source of sulfide and also the structure directing ligands through manipulation of growth and nucleation temperature; 2. While it is well known that the photo thermal conversion efficiency in Cu2-XS nanoparticles are usually less effective when compared to the Gold nanosystem, however, the plasmon properties in Cu2-xS are due to carrier holes which can be easily varied through control of the stoichiometry. This will be accomplished by taking advantage of Cu+ ion mobility in Chalcogenides, and its surface redox reactions with soluble amines to optimize the plasmonic properties and finally, the encapsulation of the Cu2-XS nanorods with folic acid conjugated heparin will enhance the matrix mobility and targeting ability for tumor cells and photo thermal conversion efficiency. Folic acid , the soluble form of vitamin B, targets tumors in a similar manner to monoclonal antibodies, as foliate receptors (FRs) are overexpressed in more than 40% of human tumors and are generally absent in healthy cells . The heparin will enhance the matrix transport properties in biological fluid or simulated body fluid through coating on the surface of the copper sulfide. If the proposed research is successfully carried out, a new matrix will emerge for targeted delivery to cancer cells and ablation of cancer cells more so in areas where surgical procedure or radiation therapy has limited success.
s The proposal aim to develop a simple process to fabricate cation deficient copper sulfide nanorods, Cu2-XS, that can be effectively optimized for high photo-thermal conversion efficiency in the Near infrared region using surface redox chemistry. The Cu2-XS will be encapsulated in folic acid conjugated heparin to form a matrix that will have the capacity to target cancer cells, provide better transport property in physiological fluid and show the ability to kill cancer cells when exposed to laser light in the near infrared region. The matrix will be an effective agent for targeting cancer cells and killing cancers cells especially in areas where conventional methods or surgical procedures are not as effective.
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