NANOMEDICINE “ Tiny ” brings a plethora for lifePREETHI SRIDHARANIV M.Sc. (BIOTECHNOLOGY)ANNAMALAI UNIVERSITYANNAMALAI NAGAR
NANOMEDICINE The science and technology of diagnosing, treating and preventing disease and traumatic injury, of relieving pain and of preserving and improving human health, using molecular tools and molecular knowledge of the human body.
SOLUBILITY AND BIOAVAILABILITY ENHANCEMENT Up to 50% of existing drugs are insoluble Thus , bioavailability is very poor Micronization of insoluble drugs Wet-milling process Increased solubility and dissolution rate Enhanced Bioavailability
Magnetic resonance imaging (MRI) Uses a combination of a large magnet , radio frequencies and image reconstruction software to produce detailed images of organs and structures - Non-invasive - High resolution - No ionizing radiation Usually superparamagnetic particles are used
Advantages of NP-based MRI contrast agents• Create image contrast enhancement• Prolonged retention in circulation• Tumor targeting• May also carry anti-tumor agent (―Theragnostics‖) MRI of melanoma tumors before and after administration ofcontrast agents
Computed tomography (CT) Tomography is a ―splicing‖ of the body into various sections and planes Mainly used in the diagnosis of lung diseases(tuberculosis) Ionized NPs are instilled intrabronchially Contrast materials- NC70146 (1-ethoxycarbonyl)((3,5- acetylamino) -2,4,6- triiodobenzoate))-nanoparticle stabilized by surfactant Iodinized nanoparticles instilled into the small airways were
Positron Emission Tomography (PET) Diagnostic application that involves the acquisition of physiologic image based on the detection of radiation from the positron Positron emission tomography (PET) using 18F fluorodeoxyglucose (FDG) has been used successfully in the diagnosis of various cancers Advantages of NPs on PET Using nanoparticles with PET allows the quantitation of PET and the multifunctionality of nanoparticles to be taken advantage Deliver large number of imaging agents to molecular targets to achieve high sensitivity Different types of imaging agent to produce multimodality
Lab on chip (LOC) Lab on chip helps in disease diagnosis
Miniature Imaging Devices Imaging has developed a pill containing a miniature video system. When the pill is swallowed, it moves through the digestive system and takes pictures every few seconds. The entire digestive system can be assessed for tumors, bleeding, and diseases in areas not accessible with colonoscopies and endoscopies Nanoprobes (miniature machines) can attach themselves to particles in the body (e.g., antibodies) and emit a magnetic field.
PASSIVE TARGETING Passive targeting involves the preparation of drug carrier complex that can avoid elimination due to body defence mechanisms The complex will keep circulating in the blood stream and allow itself to be taken to the target receptor by some body property(pH, temperature etc) Nanoparticle systems exploit characteristics of tumor growth for the use of a passive form of targeting
ENHANCED PERMEABILITY AND RETENTION (EPR ) EFFECT• Various anatomical and functional abnormalities in tumor cells causes extravasation(“angiogene sis”), and other factors including poor lymphatic clearance cause retention of macromolecules – the phenomenon called EPR.• It is now the “Golden Mean” in anti-cancer drugs• Though of high significance with high MW drugs, this is not applicable to low MW ones for obvious reasons
FACTORS AFFECTING THE EPR EFFECT OF MACROMOLECULAR DRUGS IN SOLID TUMOR Active angiogenesis and high vascular density Extensive production of vascular mediators that facilitate extravasation, including Bradykinin nitric oxide VPF/VEGF prostaglandins collagenase (matrix metalloproteinase, MMP) Defective vascular architecture: for example, lack of smooth muscle layer cells, lack of or reduced receptors for angiotensin II, large gap in endothelial cell– cell junctions, anomalous conformation (branching or stretching etc.). Impaired lymphatic clearance of macromolecules and lipids from
Polymer conjugates, in EPR context, have many upsides such as higher T1/2, better solubility, receptor mediated drug targeting and better quality of patient life While accelerated EPR can improve drug delivery and faster treatment, suppression of EPR is another approach, causing necrosis of tumor cells
ACTIVE TARGETING• On the horizon are nanoparticles that will actively target drugs to cancerous cells, based on the molecules that they express on their cell surface• Active targeting or Ligand based targeting• Specific biological processes such as Ligand-receptor recognition is used to accumulate the drug in the tumor cell• Ligands /homing devices – antibodies, peptides, vitamins and sugars.
Two important qualities of an active targeting system• Specificity of theligands onto thereceptors• Capacity todeliver therequired dose ofdrug for requiredperiod of timeSEM RESULTSSHOWING THEENDOCYTOSIS OF NPTARGETED ACTIVELY
SUSTAINED DRUG DELIVERY Controlled drug delivery is one which delivers the drug at a predetermined rate, for locally or systemically, for a specified period of time. Advantages Total dose is low. Reduced GI side effects. Reduced dosing frequency. Better patient acceptance and compliance. Less fluctuation at plasma drug levels. More uniform drug effect Improved efficacy/safety ratio
Nanorobots What are they? Nanorobots are nanodevices To repair or detect damages and infections. Exfuse themselves“Athrough human excretory microscopic machine roamingthrough the bloodstream, injecting system.or taking samples for identificationand determining the concentrationsof different compounds"
Nanorobots – Features The powering of the nanorobots. Other sources of energy . Will be having onboard computers. Size of 0.5-3 micrometers. Carbon is the primary component. Self-replication They will be able to distinguish between different cell types by checking their surface antigens. Virus detector
Nanorobots – functional requirements A navigational network has to be installed. This will enable the physician to keep track of the various devices in the body Nano-tracking may be able to detect tumors that are a few cells in size. (Alivisatos, 2001)A single inhaled nanorobot reaches, deeply inspired into the lungs and attaches to the tissue surface
DENTAL ROBOTS A mouthwash full of smart nanomachines could identify and destroy pathogenic bacteria while allowing the harmless flora of the mouth to flourish in a healthy ecosystemFour remote-controlled nanorobots examine and clean the subocclusal surfaces of a patients teeth, near the gumline.
Emergency Management: The clottocyte concept Clot-inducing medical nanorobots with fully-deployed CLOT-INDUCING MEDICAL netting capable of NANOROBOTS ARE SHOWN IN VARIOUS STAGES OF CLOT-NETTING embedding growing DEPLOYMENT. clot with red cells and fibrin strands
CLOT-INDUCING MEDICAL A REAL LIFE PICTURE OF ERYTHROCYTES TRAPPEDNANOROBOTS WITH FULLY- IN THE FIBRIN MESHWORKDEPLOYED NETTING ARE SHOWN OF A CLOTEMBEDDED IN A PATCHLIKE GROWINGCLOT WITH RED CELLS AND FIBRINSTRANDS INVOLVED (A CLOSER
The blue, octopus-like nanobot is one of billions of brain cell enhancers. Thecentral sphere houses a computer, with a storehouse of information equal tomany large libraries
Surgical Robotics Instead of manipulating surgical instruments, surgeons use their thumbs and fingers to move joystick handles on a control console to maneuver two robot arms containing miniature instruments that are inserted into ports in the patient. The surgeon’s movements transform large motions on the remote controls into micro-movements on the robot arms to greatly improve mechanical precision and safety A third robot arm holds a miniature camera, which is inserted through a small opening into the patient. The camera projects highly magnified 3-D images on a console to give a broad view of the interior surgical site. (The daVinci Surgical Robotics System)
Nanoengineered Vaccines Engineer artificial / synthetic NPs viruses Safe NP Less toxic than other adjuvants Cost-effective Enhance solubility/delivery of Dendritic Cell (APC) IFNg IgG2a vaccine components B cell IgG1, IgM, Co-delivery of antigen/adjuvant MHC II Th2 IL-4 IgA, IgE MHC I Improve cell uptake and IL-4, IL-5 CD4+ IL-6, IL-10 Th1 T cell CD8+ trafficking T cell IL-2, IL-3, IFNg, TNFa NP surface can be Humoral Responses functionalized Cellular Responses Cell-targeting
DiOC18 NPs in DCUptake of NPs BY DC Study performed at NIH/NIAID/VRC ENTRY OF HIV INSIDE THE CEL
HIV Vaccine Concept A DC-targeted nanoparticle with conserved proteins Tat (1-72) and Gag p24 to generate protective Th1, CTL, and neutralizing antibody NIH-NIAID R01 AI058842 response s that may be further enhanced by co- delivery of Adjuvants (PRLs) Dendritic Cell Toll-like Receptor (TLR-9) MHC I DC Mannose Receptor Tat (1-72) PEG Adjuvant Mannopentaose (DC targeting) (PRL) Gag p24Tat & Gag p24 antigens: conserved; critical; CTLs detected in LTNPs
Achievement And Futureprospects for Nanomedicine: 1st generation product (2000)a) Dispersed and contact nanostructure Ex-:colloidsb) Product incorporating nanostructure Ex-:Polymer,nanostructured metal 2nd active nanostructure (2000-2005)a) bio-active, health effect Ex-:targeted drugs,biodevicesb) Physico chemical active adaptive structure Ex-:amplifier, actuators 3rdNanosystem (2005-2010)a) Guided assembling Ex-:robotics, evolutionary biosystems 4th Molecular nanosystems(2010-2020)a) Ex-: molecular devices ‘by design’
CONCLUSION The next BIG thing is really “small”FUTURE NANOHumanoid shapednanorobotsRespirocytes: Artificial RBC