This document discusses the use of nanoparticles in cancer diagnosis and treatment. It introduces several types of nanoparticles that can be used, including nanoshells, dendrimers, quantum dots, superparamagnetic nanoparticles, nanowires, nanodiamonds, and nanosponges. Nanoshells and dendrimers are highlighted as promising for targeted drug delivery. The document also discusses magnetic resonance imaging contrast agents, including both paramagnetic gadolinium agents and superparamagnetic iron oxide nanoparticles, which can enhance MRI images and improve cancer diagnosis.
2. Introduction
⢠Nanotechnology promises changes in many
significant areas of medicine, material science,
construction, etc. In medicine advanced
nanostructures, such as functional
nanoparticles, dendrimers, fullerenes, carbon
nanotubes and semiconductor nanocrystals
have been exploited for drug delivery,
diagnostics and treatment of diseases at the
molecular level.
3. NANOMEDICINE
⢠Specific application of nanobiotechnology to
nano and molecular scale design of devices for
the prevention, treatment, and cure of illness and
disease is called nanomedicine.
⢠In cells, proteins are nanomachines that act as
transporters, actuators, and motors. They are
responsible for specific monitoring and repair
processes. In this role nanoparticle is usually a
nano-sized polymeric colloidal particle with the
drug either encapsulated within the polymer or
conjugated onto its surface.
4. ⢠Nanoparticle-based therapeutics â
nanopharmaceuticals â are colloidal particles of 10 to
1000 nm (1 micron) that are diverse in size, shape and
composition. Therapeutic delivery systems are
designed to deliver a range of therapeutic agents,
including drugs, proteins, vaccine and plasmid DNA for
gene therapy, by exposing target cells to their payload.
This requires the carrier to enter cells where, once
internalized, the therapeutic agent is released through
vehicle degradation and diffusion mechanisms.
⢠Current nanoscale delivery systems are divisible into
two major categories: surface modification systems
designed to prevent immune response or promote cell
growth, and particle-based systems designed to deliver
therapeutics to cell and tissues.
5. Nanomaterials used for cancer
diagnosis and treatment
⢠Nanoshells
⢠Dendrimers
⢠Quantum dots
⢠Superparamagnetic Nanoparticles
⢠Nanowires
⢠Nanodiamonds
⢠Nanosponges
6. One of new findings for nanoscale drug delivery in diagnosing and treating cancer are
nanoshells â gold-coated silica. These nanoshells, set in a drug-containing tumor-targeted
hydrogel polymer, injected into the body, accumulate near tumor cells. When heated with
an infrared light, the nanoshells selectively absorb a specific infrared frequency, melting the
polymer and releasing the drug payload at a specific site. They are designed for specific
targeting micrometastases, tiny aggregates of cancer cells too small to remove with a
scalpel.
7. ⢠Another nanoscale drug delivery system can be created with
the use of dendrimers. Dendrimer is precisely constructed
molecule built on the nanoscale in a multistep process
through up to ten generations and from 5 to 50 nm in scale .
⢠A dendrimer is typically symmetric around the core, and
often adopts a spherical three-dimensional morphology.
Drugs and recognition molecules can be attached to their
ends or placed inside cavities within them.
8. ⢠The dendritic multifunctional platform is ideal to combine
various functions like imaging, targeting, and drug transfer into
the cell.
⢠Quantum Dots
⢠Quantum dots are semiconductors, the most commonly used
cadmium selenide capped by zinc sulphide (CdSe/ ZnS). The size
of quantum dots range from 2 to 10 nm in diameter and these
are composed of 10â50 atoms, containing electronâhole, pairs
to a discrete quantized energy.
ď How Quantum Dots Work?
⢠When energy is applied to an atom, electrons are energised and
move to a higher level. When the electron returns to its lower
and stable state, this additional energy is emitted as light
corresponding to a particular frequency. QDs work in much the
same way but a QD crystal acts as one very large atom. The
energy source used to stimulate a QD is commonly ultraviolet
light. The frequency or colour of light given off is not related to
the material used in the quantum dot, but by the size of the QD.
9. ⢠Superparamagnetic Nanoparticles
⢠Iron oxide particles (Fe3O4) are referred as magnetic
nanoparticles and developed as superparamagnetic
nanoparticles.
⢠The sizes of the nanoparticles are less than 10 nm in diameter.
These nanoparticles are having potential application in magnetic
resonance imaging. Many reports revealed that
superparamagnetic nanoparticles can be functionalized with
other type of nanoparticle, so as to permit specific tumor
targeting.
⢠These are also having importance in the use of magnetic fields
to localize magnetic nanoparticles to targeted sites, a system
known as magnetic drug targeting.
⢠Superparamagnetic nanoparticles can be modified by improving
the solubility and specificity of iron oxide particles. Iron oxide
nanoparticles can also be used in imaging techniques that can
selectively image proliferating cells in vivo can provide critically
important insights of tumor growth rate, degree of tumor
angiogenesis, effectiveness of treatment and vigor normal cells.
10. ⢠Nanowires
⢠Nanowires are nanoparticles with diameters of only a
few nanometres and extended lengths. Predictably, the
length and width ration is extremely large making them
effectively one-dimensional structures. These are
revolutionized innovative compounds these would be
used to link together tiny components into extremely
small circuits. These nanowires are purported to have
functions in monitoring brain electrical activity without
having to use a brain probe and violating the brain
parenchyma.
11. ⢠Nanodiamonds
⢠Nanodiamonds are synthesized in 1962 by detonation and
also can be prepared by covalent and noncovalent
modification to absorb or graft a variety of functional groups
and complex moieties, including proteins and DNA. These are
attractive agents for use in biological and medical applications
largely due to their greater biocompatibility than other carbon
nanomaterials, stable photoluminescence, commercial
availability and minimal cytotoxicity.
⢠Nanodiamonds can be used for cell labeling and tracing
because they do not interrupt cell division or differentiation,
have minimal cytotoxicity, and are easily functionalized with
proteins and other markers for targeting purposes.
Nanodiamonds have successfully have been used as
biomarkers or tracers to label or trace HeLa cells, lung cancer
cells, and murine fibroblasts.
12. ⢠Nanosponge
⢠Nanosponge is like a three-dimensional network or scaffold. Its
backbone is a long length of polyester and the size is of about virus.
Nanosponge is mixed in solution with small molecules called cross-
linkers that act like tiny seizing hooks to tie up different parts of the
polymer together. The net effect of this arrangement is to form
spherically shaped particles filled with cavities where drug molecules
can be stored and then injected into the body. This tiny sponge
circulates around the tumor cell until they encounter the surface to
sustain releasing their drug cargo. Nanosponge is three to five times
more effective at reducing tumor growth than direct injection. The
targeted delivery systems of nanosponge have several basic
advantages like, the drug is released at the tumor instead of circulating
widely through the body, it is more effective for a given dosage . The
nanosponge should have basic features such as fewer harmful side
effects because smaller amounts of the drug will come into contact
with healthy tissue.
13. MRI Contrast enhancement and
diagnosis kits
Basic Principles of Magnetic Resonance Imaging
Contrast Agents in MRI
Types of gadolinium contrast agents
Superparamagnetic contrast agents
14. Basic Principles of Magnetic
Resonance Imaging
⢠Magnetic resonance imaging is an imaging modality which
is primarily used to construct Images of the NMR signal
from the hydrogen atoms in an object.
⢠In medical MRI, radiologists are most interested in looking
at the NMR signal from water and fat, the major hydrogen
containing components of the human body .
⢠MRI utilizes the strong static homogenous magnetic field
generated by the magnet. When the high frequency
magnetic field is applied to the subject placed in the
homogeneous static magnetic field, it excites proton
nuclear spins within the patient's tissues.
⢠The excited proton spins rotate at a rate dependent upon
the static magnetic field. As they flip, they emit radio
frequency signals, referred as magnetic resonance signals.
15. Contrast Agents in MRI
MRI signal strength depends on the longitudinal (T1) and
transverse (T2) relaxation time of water protons, the difference in
the relaxation times causes different contrasts in MRI images . To
maximize image quality, MR contrast agents are often needed to
decrease T1 and T2 relaxation times. Several materials have been
recently developed to enhance the image contrast and diagnostic
accuracy of MRI. MRI contrast agents can be divided into two main
categories of paramagnetic and super paramagnetic compounds.
Paramagnetic contrast gents, also called T1 or positive contrast
agents, are usually composed of Gadolinium3+ or Mn2+, which
generates positive signals on T1-weighted images.
Superparamagnetic contrast agents, also called T2 or negative
contrast agents, are usually constructed with iron oxide, which
generates negative signal on T2 weighted images.
16. ⢠Paramagnetic Agents
⢠Currently paramagnetic metal ions are used as contrast
agents in MRI. These materials are metals with unpaired
electrons in their outer shell (transition and lanthanide
metals). The two main and widely used compounds of this
class are Gadolinium and manganese
Gd-based magnetic resonance contrast agents (GBCAs) for
molecular imaging
⢠Gadolinium Gd(III) chelates
⢠Macromolecular Gd(III) complexes
⢠Dendrimer
⢠Gadolinium-Based Hybrid Nanoparticles
⢠Biodegradable macromolecular
⢠Liposomal particles
⢠Targeted contrast agents
17. Types of gadolinium contrast agents:
⢠Extracellular fluid agents: Dotarem, Magnevist, Omniscan,
OptiMARK, and Prohance
⢠Blood pool agents (intravascular agents): Polydisulfide Gd(III)
complexes have relatively long blood circulation time are
gradually into small compounds that are rapidly excreted
through the kidney filtration converted. The use of
biodegradable macromolecular contrast agents in MRI
imaging cardiovascular disease and cancer, and to evaluate
the response to treatment
⢠Organ-specific agents: Tetra-P-aminophenylporphyrin (TPP)
was conjugated with gadolinium diethylenetriaminepen-
taacetic acid (DTPA) (Gd2(DTPA)4TPP) could be a useful in MR
imaging contrast agent with an specific tumors contrast agent.
A new class of metal-loaded nanoparticles has developed that
have potential as contrast agents for medical imaging.
18. Superparamagnetic contrast agents
⢠Several classes of magnetic iron oxide nanoparticles, also
known as superparamagnetic IONPs (SPIO) and ultrasmall
SPIO (USPIO) developed in 1980s, has been approved by FDA
(e.g., Feridex) for clinical applications with capabilities of
traditional âblood poolâ agents.[20, 21] The important
properties of cell phagocytosis of magnetic nanoparticles has
expanded the applications of contrast enhanced MRI beyond
the vascular and tissue morphology imaging, enabling many
novel applications of magnetic IONPs for MRI diagnosis of
liver diseases, cancer metastasis to lymph nodes, and in vivo
tracking of implanted cell and grafts with MRI.