Biomedical Nanotechnology Lecture 11: Nanomaterials for Cancer Diagnosis PDF

BIOMEDICAL NANOTECHNOLOGY LECTURE 11: NANOMATERIALS FOR CANCER DIAGNOSIS Dr.P.GOPINATH DEPARTMENT OF BIOTECHNOLOGY 1  Contents What is cancer? Nanomaterials for cancer diagnosis Qu...

BIOMEDICAL NANOTECHNOLOGY LECTURE 11: NANOMATERIALS FOR CANCER DIAGNOSIS Dr.P.GOPINATH DEPARTMENT OF BIOTECHNOLOGY 1  Contents What is cancer? Nanomaterials for cancer diagnosis Quantum dots Computed tomography Magnetic resonance imaging 2  Cancer & tumor  Cells that continue to replicate, fail to differentiate into specialized cells, and become immortal.  Malignant: A tumor that grows indefinitely and spreads (metastasis)--also called cancer: kills host  Benign: A tumor that is not capable of metastasis: does not kill host 3  Types of cancer Carcinoma: arising from epithelial tissue, such as glands, breast, skin, and linings of the urogenital, digestive, and respiratory systems (89.3% of all cancers) Sarcoma: solid tumors of muscles, bone, and cartilage that arise from the embryological mesoderm (1.9% of all cancers) Leukemia: disease of bone marrow causing excessive production of leukocytes (3.4% of all cancers) Lymphoma, Myeloma: diseases of the lymph nodes and spleen that cause excessive production of lymphocytes (5.4% of cancers) 4  Etiology of cancer Genetic factors: mutations, translocation, amplifications Environmental factors: UV, chemicals, viral infections conversion of proto-oncogenes (potential for cell transformation) to oncogenes (cell transformation) alteration in tumor suppressor genes 5  Cell growth Control of cell growth Growth-promoting Growth-restricting Proto-oncogenes Tumor-suppressor genes 6  Molecular basis of cancer Uncontrolled cell growth Conversion of proto-oncogenes to oncogenes Altered tumor-suppressor genes 7 8 T -cells Vs Cancer cells 9 10  Biomarker research status ? ? Hmmm!! I see you have abnormal ‘biomarkers’ TODAY PSA levels. You might have some ? ? problems in your prostate. We must PSA check for cancer 11  Biomarker Research Status Oh!! You have abnormal PSA levels. Also, your levels of BM1,BM2,BM3 are off, and BM4 levels are subnormal. You are starting to develop prostate cancer of the A phenotype. But don’t worry your BM5 is BM5 fine, so metastasis hasn’t occurred yet. Let’s start treatment BM1 BM2 BM4 PSA THE FUTURE BM3 12 Nanodevices can make cancer tests faster and more efficient Patient A Patient B https://www.cancer.gov/ https://www.nano.gov/ 13  What are Quantum Dots (QDot)? Highly fluorescent, nanometer-size, single crystals of semiconductor materials Size of the nanocrystal determines the color Size is tunable from ~5-15 nm ( 3%) Size distribution determines the spectral width 14  Quantum dots --Medical imaging Optical properties of nanoparticles depend greatly on its structure. Particularly, the color (wavelength) emitted by a quantum dot (a semiconductor nanoparticle) depends on its diameter. The quantum dots (QD) can be injected to a subject, and then be detected by exciting them to emit light Nano Letters 2008., Vol. 8, pp3887-3892 Solutions of CdSe QD’s of different diameter Source: Department of immunology, University of Toronto Imaging of QD’s targeted on cellular structures 15 Qdot Conjugates are Engineered Core Nanocrystal (CdSe) - Determines color Inorganic Shell (ZnS) – Improves brightness and stability Organic Coating - Provides water solubility and functional groups for conjugation. Biomolecules -Covalently attached to polymer shell - Immuoglobulins (Abs) - Receptor ligands 15 - 18 nm - Oligonucleotides 16  Quantum Dots Ultraviolet Ultraviolet light off light on Quantum dot Quantum Quantum dots bead dots emit light https://www.cancer.gov/ https://www.nano.gov/ 17 Quantum dots can find cancer signatures Quantum dot beads Cancer cells Healthy cells Cancer cells Quantum dot beads Healthy cells https://www.cancer.gov/ https://www.nano.gov/ 18 Excellent brightness and photo-stability High level Her 2/neu expression in SK- BR-3 cells Quantum dots is up to 50x brighter. Low level of Her 2/neu expression in MDA-MB-231 cells Organic dye is undetectable. 19  Sharp and distinguishable peaks enable multi-color detection Minimal (1000 nm, with fluorine, followed by pyrolysis at a 1000 C. This treatment cut the SWNTs into smaller, ultra-short, nanotubes (20–100 nm long) and caused them to be pitted; that is, missing carbon atoms on their surface. 36  Magnetic resonance imaging The pyrolized nanotubes, which the investigators called ‘US-tubes’, were sonicated in an aqueous solution containing GdCl, which resulted in the binding of Gd+3 ions to the pitted sections of the tubes. In order to use the Gd tubes in relaxation studies, the investigators added various surfactants to the medium, which produced water suspensions of the material, Gd 3+n @US-tubes. Advantages: Low concentrations of Gd3+@US-tubes could be used to bring about the same level of MRI enhancement as produced by other agents, which, since lower concentration of the CA would need to be administered, would be beneficial to the patient. 37 Gadonanotubes for MRI 38  Magnetic nanoparticles for MRI contrast enhancement Surface Modification Techniques for Magnetic Nanoparticles a) Surface coating of magnetic NPs for direct attachment to cells --- -- ---- + + + Cell membrane is –vely -- -- + + + + + + + + charged and will bind to -- - -- +vely charged particles Iron oxide +vely charged +vely charged through electrostatics. nanoparticles polyelectrolyte Iron oxide nanoparticles 39 Magnetic nanoparticles for MRI contrast enhancement Surface Modification Techniques for Magnetic Nanoparticles b) Attachment of molecules for conjugation of antibodies R OEt OH R OH + EtO-Si-(CH2)3-R O -Si-(CH2)3-R OEt OH R R = NH2, SH, CHO R Antibodies are conjugated through the R- functional group 40  Magnetic nanoparticles for MRI contrast enhancement Surface Modification Techniques for Magnetic Nanoparticles c) Gold coating to form core-shell morphology Iterative addition Gold surface can be readily HAuCl4 + conjugated with various Hydroxylamine biomolecules Iron oxide NPs Iron oxide-gold Core-shell NPs 41 42 Pregnancy test for man??? 43  Summary What is cancer? Nanomaterials for cancer diagnosis Quantum dots Computed tomography Magnetic resonance imaging 44