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An introduction to future drug delivery system. By: Ali khorramdust. The prefix ‘ nano ’ comes from the Greek word ‘ nanos ’ meaning ‘a dwarf’.Hence,’nanotechnology ’ Might well simply mean a technology to do with ‘small’ things
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An introduction to future drug delivery system By: Ali khorramdust
The prefix ‘nano’ comes from the Greek word ‘nanos’ meaning ‘a dwarf’.Hence,’nanotechnology’ • Might well simply mean a technology to do with ‘small’ things • Nanotechnologies are the design,characterization,production and application of structures • The size range of interest between a few nanometers and 100 nm is one where many interesting • Things happen. • They can easily transferred through blood vessels and interact with targeted tumor-specific • Proteins both on the surface of and inside cancer cells. • Inadequate drug concentrations reaching the tumor,and the limited ability to monitor therapeuti • Responses.poor drug delivery to the target site leads to significant complications. • Nanotechnology and nanomedicine has exploited the possibility of designing tumor-targeted • Nanocarries able to deliver radionuclide payloads in a selective manner to improve the efficacy • And safety of cancer imaging and therapy. • The major nanocarries include nanopores,carbonnanotube,nanoparticles,dendrimers,quantum • Duts,liposomes,and… • .
Nanotubes: • Nanotubes are smaller then nanopores. • About half the diameter of a molecular of DNA also help to identify DNA changes associiated • With cancer cells. • It helps to exactly pin point location of the changes.mutated regions associated with cancer are • First tagged with bulky molecules.using a nanotupetip,resembling the needle on a record player • The physical shape of the DNA can be traced.a computer translates this information into • Topographical map. • Quantum Dotes(QD): • These are tiny crystals that glow when these are stimulated by ultraviolet light. • The latex beads filled with these crystals when stimulated by light,emiit the color that lights up • The sequence of interest. • serving as sort of spectral bar code.
Nanotube: Quantum Dots:
Nanoshells(NS): • These are another recent invention.NS are miniscule beads coated with gold. • The most useful nanoshells are those that absorb near infrared light that can easily penetrate • Several centimeters in human tissuses. • Absorption of light by nanoshells creates an intense heat that is lethal to cells. • In laboratory cultures the heal generated by the light-absorbing nanoshells has successfully • Killed tumor cells while leaving neighboring cells intact. • Liposomes: • Liposomes are self-assembling spherical closed colloidal structures composed of lipid bilayers • That surround a central aqueous space. • Liposome based formulations of several anticancer agents have been approved for the • Treatment of metastatic breast cancer and Kaposi’s sarcoma.
Caltilevers: • Tiny bars anchored at one end can be engineered to bind to molecules associated with cancer • It would be possible to tell whether the cancer molecules are present and hence detect early • Events in the development of cancer cells. • Dendrimer: • A number of nanoparticles that will facilitate drug delivery are being developed. • It is hoped dendrimers can be manipulated to release their contents only in the presence of • Certain trigger molecu;es associated with cancer.following drug releases the dendrimers may • Also report bacj whether they are successfully killing their targets. • Nanopores: • Nanopores(holes)allow DNA to pass through one strand at a time hence DNA sequencing can • Be made more efficient. • The passage of DNA through a nano pore can be used to decipher the encoded information • Including errors in the code known to be associated with cancer.
Recent advances in nanothechnology in cancer Treatment: • Fluorescent Nanoparticles: • The diagnosis and treatment of cancer have been greatly improved with the recent • Developments in nanotechnology one of the promising nanoscale tools for cancer diagnosis is • Fluorescent nanoparticles(NPs) such as organic dye-dope NPs quantum dots and upconversion • NPs that enable highly sensitive optical imaging of cancer at cellular and animal level. • Monoclonal antibodies and Nanobodies: • In the past decades the mainstay of systemic therapy for solid and haematology malignancies • Was chemotherapy nevertheless this modality has the drawbacks such as drug resistance and • Eliciting sever cytotoxicity in normal tissue. • The therapeutic monoclonal antibodies(mAbs) are deemed to be a class of novel agents that • Can specifically target and disrupt molecular pathways underlying tumorigenesis.themAbs are • Produced by a single clone of B-cells and are monospecific and homogeneous. • The recombinant antibodies have been reduced in size rebuilt into multivalent molecules • And fused with different moities such as radionuclides toxins enzymes. • Focuses on implementation of the mAbs and nanobodies fragments for cancer therapy.
3)Nanomedicine: • Nanothechnology has been extensively merging into biomedical research to develop a new • Research field Nanomedicine. • The effects of gastrin messenger RNA(mRNA) down-regulation on growth of human pancreatic • Cancer Gastrin expression was examined in human pancreatic cancer cell lines by reverse • Transcriptase-polymerase chain reaction and peptide expression was assessed by immunocytoche • misteryGastrin was down-regulated using either stable transfection of an antisense gastrincDNA • Or 1 of 3 shRNA(short hairpin RNA) constructs Stable transfection in gastrin antisense or shRNAs • Into BxPC-3 cells resulted in clones with more than 90% reduction in gastrin mRNA • Immunofluorescence analysis confirmed that gastrin peptide levels were decreased in antisense • And shRNA tumors. • 4)Nanomicelles: • Emerging nanotechnology has already developed various innovative nanomedicines • Self-assemblies of block copolymers are promising nanomedicines for targeted drug delivery and • Imaging stimulus-responsive targeted nanomicelles are designed to release drugs on based on • Stimuli such as PH temperature redox potential magnetism and ultrasound.
5)Carbon Nanotubes: • A vast majority of applications are based on CNTs raging from miniaturized biosensors to organ • Regeneration Nevertheless the complexity of biological systems poses a significant challenge in • Developing CNT-based tissue tissue engineering applications alikhorramdust focuses on the • Recent developments of CNT-based tissue engineering where the interaction between living • Cells cells/tissues and the nanotubes have been transformed into a variety of novel techniques. • Functional analyses of water-dispered carbon nanohorns with antitumor activity were • Performed to explore their potential as drug carrier for local cancer chemotherapy.water- • Dispered carbon nanohorns were prepared by adsorption of polyethylene glycol-doxorubicin • Conjugate(PEG-DXR) onto oxidized single-well carbon nanohorns(oxSWNHs).PEG-DXR bound • Ox SWNHs were administered intratumorally to lung cancer-cell NCI-H460-bearing mice. • In vitro studies showed that carboplatin-filled CNTs inhibited growth of bladder cacer cells • Whereas unfilled opened CNTs barely affected cancer cell growth
6)Gold Nanoparticles: • Nanotechnology has used to provide advanced biomedical research tools in diagnostic imaging • And therapy which requires targeting of nanoparticles(NPs) to individual cells and subcellular • Compartments. • Results show that the cellular uptake of gold NPs is dependent on their size and surface property • The NPs were transported in vesicles of 300-500 nm diameter within the cytoplasm.the average • Velocity and diffusion coefficient of the vesicles containing NPs were 10.2(+/-1.8) microm/hr • And microm 2/hr respectively Analysis of the time dependent intracellular spatial distribution of • The NPs demonstrated that they reside in lysosomes within 40 minutes of incubation. • 7)Radioprotection by nanoparticles: • Radiolysis of water generates a series its radical decomposition products that inactivate • Enzymes and damage cellular lipids proteins and DNA postirradiation protection is another • Approach to reduce or reverse deleterious effects after exposure to ionizing radiation • Fullerenes (C60) diminished toxicity of radiation on zebra fish embryos by reducing generation • Of reactive oxygen species fulleronols (C60[OH]X) protected unicellular eukaryotes organisms • Against gamma radiation Cerium oxide nanoparticles(nanoceria) increased longevity of cells by • Reducing hydrogen peroxide and ultraviolet radiation induced injury Autoregerative reaction • Cycle Ce3+↔Ce4+ occurs on the surface of the ceria nanoparticles:changing oxidation state • From Ce3+ to Ce4+ might scavenge free radicals produced by radiation.
Monitoring toxicity in real time using novel impedance technique: • Interaction of mammalian cells with surfaces and focus on the kinetic aspects of this • Phenomenon is of great for science Cell attachment is an important parameter to assess cancer • Cell potential for metastasis and tumor healing caused by their dynamic interaction with • Sabstrates and drugs. • Cell-to-cell communications were studied by injecting a dye lucifer yellow to a single cell • Through a microelectrode: electrical characteristics of the cells were measured with the electrode • And transfer of the dye from the single cell to its neighbours by cell-to-cell gap junctions was • Observed in cell monolayers. The method that applies external electrical field to sense cell • Spreading upon artificial surfaces in real time is referred to as Electric Cell-substsateImpedence • Sensing (ECIS) • Although the ECIS technique has been first described by Giaever and Keese • Measurements using ECIS of repopulation of mechanically disrupted cells in culture have been • As well suggested as wound healing assey. • The ECIS technique is becoming a well-stablished technique to study chemical and physical • Factors and other dynamic processes. • Concentration to achieve 50% inhibition was determined in fibroblast V79 cells for free metals • And quantum dots: around 6µM for Cd 98µM for Zn 154nM for red CdSe/ZnS 240 nM for green • Cd/ZnS. For the cadmium selenide and telluride quantum dots toxicity could be assigned to • Release of free cadmium.for quantum dots and gold nanoparticles were not toxicity 200nM and • 45µM.
