Nanobiotechnology in Understanding Cancer Biology-Juniper Publishers
Open Access Journal of Toxicology
Abstract
The biosynthesis of nano particles with a great deal
of effort by using a 'Green technology' that gives an innocuous,
inexpensive and environmental friendly approach has been widely used.
The technology also leads to fabricate wonder materials for biomedical
applications.
The in vitro green approaches for the reduction of metal ions furnishes a
flexible method to obtain nano particles with control over their size
and shape that can be attributed to the flexibility of changing the
medium pH and reaction temperature. This review provides an outlook on a
range of devices and tools that can make a system for detection of a
therapeutic agent and to determine its action on an intended target,
facilitating the research in diagnosis and prevention of cancer. The
validation of nano particles with these exciting approaches may serve a
strong foundation for modified chemotherapies in the next phase of
clinical trials which would lead to profound changes in oncological
practices by facilitating the realization of personalized medicines
through demonstration of safety as well as efficacy in human clinical
trials.
Keywords: Green technology; Wonder materials; Personalized medicines;
Cancer; Modified chemotherapy.
Keywords: Green technology; Wonder materials; Personalized medicines; Cancer; Modified chemotherapy
Introduction
Since the first preparation of the nano-particles
that was carried out by Michael Faraday as early as in 1857, nano has
become a flavor in the world of science. Nanoparticles, because of their
exciting phenomenon of small size and variable shapes as spherical,
wiry, tubular or sheet like has gained tremendous importance in the
areas of medical diagnostics, drug delivery, chemical industry, textile
industry and electronics. The utilization of this technology for the
preparation of nano based products in area of research and development
is growing at a great pace and is still expected to grow further in the
coming years. The revolutionary impact of nanoscience in today's world
is associated with the unforeseen hazards of these particles related to
its method of synthesis.
The intersection of nanotechnology and biotechnology
has led to a fairly new area of technology; Nano biotechnology. This new
area of research has been used in the development of nanomedicine that
covers health care related areas of nanoscience and technology and
serves structured nanodevices to analyze the specific biological system.
Top-down and bottom-up approaches
The synthesis of nanomaterials and effective
fabrication of nanostructures follows two basic approaches; the top down
approach involves successive cutting of larger parts to get nano sized
particles of smaller and smaller dimensions. Bottom up approach follows
building of material from atoms or molecules or by clusters. However,
the disadvantage associated with the top down approach is the structural
damage leading to imperfection of surface structure and patterns.
Bottom up approaches provides a better chance to form nano structure
with fewer defects although; the process frequently in Nanotechnology is
not a newer concept.
Nano synthesis: a green remedy
A remarkable area of nanoresearch is often concern
with the global environment. A great deal of effort has been put on that
provides a better platform for the biosynthesis of nano particles by
using plants [1]
that are more innocuous, inexpensive, and environmentally friendly as
they do not leave hazardous residues to pollute the atmosphere [2-6].
Although, the chemical method of synthesis requires less time for the
fabrication of large quantity of nano particles, but are considered
toxic and often lead to products that are non-eco-friendly [7].
In recent years, the in vitro green approaches for the reduction of
metal ions provides a flexible, method to obtain nano particles with
control over their size and shape that can be attributed to the
flexibility of changing the medium pH and reaction temperature [8].
Variety of different plant species in combination with acid and salts
of metals can be used to reduce ions of gold, copper, silver, platinum,
iron and many others [9].
Current appearance in cancer diagnosis and drug delivery
Facilitating the research in diagnosis and prevention
of diseases, Nanotechnology offers a range of devices and tools that
can make a system for detection of a therapeutic agent and to determine
its action on an intended target. In recent years, nanotechnology has
become a boon in cancer research by helping the oncologist to spot the
cancer in early stages by detecting biomarkers that are undetectable
through conventional detection techniques. Nanotechnology researchers
have provided nano medicine based approaches that have been considered
safe and effective treatment of cancer. Of the advances driven by
National Cancer Institute (NCI), the discrimination of a healthy and
cancerous cell by the use of photo luminescent nano particles will
enable the clinician to identify the precancerous lesions thereby
providing an early signal to reverse the premalignant changes and also
allowing a time release of an anticancer drug sequentially at a desired
location (www.cancer.gov). Tumors targeting objective has also
influenced the role of Gold Nano particles (AuNP's) by their conjugation
to Polyethylene Glycol (PEG) and unique biomarker binded antibodies on
tumor cells. The fabrication of AuNP's with PEG prevented the unwanted
aggregation and lengthened the retention time in blood by preferential
accumulation of the particles in the tumor [10].
In another study, researchers at Cornell University have figured out
the attachment criteria of gold nano particles by merging with iron
oxide into colorectal cancer cell seeking the role of antibodies that
can deliver the gold to the cancerous cell which can be heated by
passing infrared laser because of the efficient property of the tiny
particles of gold alloy which in turn will kill the cancerous cells [11].
Nano particle based drug delivery have also gain
considerable potential for effective drug delivery in cancer therapy.
The major challenge in the treatment of the disease is to get the drug
at a specific place that is needed thereby avoiding side effects to
other non-targeted organs. The limitations associated with the
chemotherapeutics used against such dreaded disease are their
non-restricted cytotoxicity in context to increasing dosage
concentration. The nano particle formulation resulted in enabling the
strategy of targeted drug delivery and these includes benefits of their
small size which allow an easy penetration into the cell membrane,
binding and stabilization of protein and lysosomal escape after
endocytosis [12]
thereby leading to the development of faster and safer medicines.
Recently, the emergence of numerous proteinic and other drugs for
targeting various cellular process have created a demand for the
development of intelligent drug delivery system [13].
To meet the requirements for intelligent release of therapeutic agents
to perform various function of detection, isolation and treatment of
diseased conditions, a smart delivery system such as stimuli responsive
nano materials will be a promising approach [14].
Carbon nano tube with its hollow structure is one of
the wonder nano material that have motivated the researchers to explore
their potential in the application of drug delivery to transport drug
molecules, proteins and nucleotides. The size and shape of these
materials allow them to enter living cells by adhering covalently or
non-covalently to the surface without causing cell damage [15].
The potential application of carbon nano tubes in biotechnology is of
much interest for exhibiting its advantages in biosensors [16], biomedical devices [17] and drug delivery systems [18].
However, the fictionalizations of CNTs is needed to reduce the chances
of cytotoxicity and improving their biocompatible properties. The
surface properties of the CNTs greatly influence their internalization
behavior into the cell that is aided by the hydrophilicity of the tube.
Also, the shorter length nano tubes are more effectively transported
across the cell than the bundled CNTs [19].
Engineering of polymeric nanostructures for drug
delivery inputs the use of a highly branched polymer known as Dendrimers
that resemble the architecture of a tree. These multi branched
macromolecules have attracted the researchers for various application in
many fields due to its low polydispersity and high functionality.
Dendrimers have offered escalating attention in scientific research
particularly in the area of biomedical and pharmaceutics as a potential
drug vehicle. A well-defined globular structure of these materials
ensures a reproductive pharmacokinetics besides causing an increased
cellular uptake of the drugs conjugated to them [20].
Mesoporous silica nanoparticles have reported
exponential increase in research and are one of the hottest areas in the
field of nanomedicine and nano biotechnology for its functional
application as biocompatible nanocarriers. With a mesoporous structure,
MSNs have been explored to treat various kind of disease parameters
including tissue engineering [21] diabetes [22] inflammation as well as cancer [23].
The unique tailor able structure of mesoporous silica nano particle
with their high surface area to large pore volume endow them to
encapsulate variety of therapeutic agent to emphasize the targeted
delivery into desired location [24]. Currently, delivery of variety of molecules of pharmaceutical interest has been appeared by employing mesoporous materials [25].
Mesoporous Silica Nanoparticle of size 50 to 300nm is considered facile
for endocytosis without cytoxicity. Materials including MCM-41, SBA-15,
SBA-1, SBA-3, HMS and MSU are groups of mesoporous biocompatibility and
release kinetics of various drugs [13] materials that have been functionalized for improving the (Figure 1).
Nanotechnology in toxicity outlook; a concern/ lacunae
Although the use of wide variety of nanostructures
continued to alter the current scenario of cancer disease and
diagnostics as a carrier system due to its biocompatibility and ability
to reduce systemic toxicity, a crucial investigation regarding the
toxicological effect of nanoparticles and the route of particle
administration as a potential source of toxicity has to be emphasized
which may arise due to its size, shape, dosage, charge as well as
surface chemistry. The effect of these Nano materials results from its
interaction particularly with the proteins that may lead to clumping of
the protein molecules and linking up of various medical conditions. The
large sized particles, once inside will move to circulation and may
accumulate in organs including liver, spleen heart and brain. Also,
direct cell to cell transfer of these particles is very unlikely as the
pores between the cells are even smaller than their size.
The absorption and opsonisation of nanomaterials or
nanoparticles by serum protein may alter the effective size of the
particles resulting in the change of an in vivo hydrodynamic diameter
which is often lager than the size of in vitro Nanoparticles. There may
be different trends of bio toxicity of nanomaterials in different
ranges. Therefore, with the explosive increase in the research of this
robust technology, it is necessary to have a concern outlook to fulfill
the biomedical demand by well controlled fabrication of nano materials
prior to be implemented in clinical practices.
Nanotechnology; validation in clinics.
The tremendous effort of the scientist towards
protective utilization of nano particle based medicines or Nano
medicines in fighting against cancer are showing promising outcomes.
Concerning the issues associated with the drug circulation time and a
localized therapy to the site of the disease, the utilization of Nano
based therapeutics have a clear benefits than the unmodified drugs.
The progress route of Nano therapeutics has already
been demonstrated in the clinic. Doxorubicin contained in a hollow
nanoparticle used to treat ovarian cancer was the first Nano based
cancer drug approved by Food and Drug Administration. Likewise, the
evidence of nanoparticle delivered clinical RNA interference (RNAi)
published in Nature [26], first demonstrated by Calando Pharmaceuticals was approved by FDA in various stages of trials.
The reduction of lung and toxillar lesion with a
nanoparticle based therapeutic whereby the particles were combined with
prostrate specific membrane antigen (PSMA) was reported by BIND
Biosciences [27].
The outcome of the trial was greater efficacy compared to a lone drug
at substantially lower doses. Furthermore, an albumin functionalized
paclitaxel formulation of Celgene's Abraxane has got recognition for its
necessary effect in the treatment of lung and pancreatic cancer along
with breast cancer therapy by FDA (The-Scientist.com).
Drs. Ciaus Radu, Owen Witte and Micheal Phelps have
designed a series of positron emission tomography (PET) at the Nano
system Biology Cancer Center. The system was used for assigning
chemotherapy to the patients such as gemcitabine, cytarabine,
fludarabine and others to treat metastatic breast cancer, ovarian, lung
as well as leukaemia and lymphomas. A bio distribution study was also
conducted in eight healthy volunteers. A nanoparticle magnetic resonance
imaging contrast agent found on the surface of newly developing blood
vessels associated with early detection of tumor was developed by Dr.
Gregory Lanza and his team at Siteman Center of Cancer Nanotechnology
Excellence, Washington University. Phase I clinical trial was performed
for assessing the utility of the agent in early detection of tumor.
A Nano sphere diagnostic company founded by Dr. Chad
Mirkin at Nanomaterial for cancer diagnostic and therapeutic center has
received approval by FDA for detecting cancer biomarkers by using Nano
sensor. A clinical study using human tissue sample was performed to
monitor low level of Prostate Specific Antigen (PSA) successfully
Nanomaterial using silica, metal, polymers as well as
carbon based particles have been demonstrated on preclinical front
which shows satisfactory results. Recently, a report on multi drug
delivery action and efficacy of nanoparticles to mediate resistance in
relapsing cancer and improving triple negative breast cancer was by a
team of researchers (The-Scientist.com). Other approaches including
layer by layer siRNA delivery for breast cancer, sequential
administration of Nanoparticles for pancreatic cancer treatment and
tumor penetrating peptides against ovarian cancer are very recent.
Thus, the validation of nanoparticles with these
exciting approaches may serve a strong foundation for modified
chemotherapies in the next phase of clinical trials which would lead to
profound changes in oncological practices by facilitating the
realization of personalized medicines through demonstration of safety as
well as efficacy in human clinical trials.
Future prospects
Dealing with the most significant issue of cancer
cells of Multi Drug Resistance (MDR) the heightened technology has shown
inimitable benefits owing to a targeted delivery with its small sized
vectors. The clinical prospects of nano materials are tremendously
affecting the treatment of malignant cells which are more likely to
possess the scene of multi drug resistance. The use of dendrimers as a
promising material in nanooncology has been proved as an ideal candidate
for delivering drugs to the tumor region, Besides this, dendrimers have
been investigated for its use in killing bacterial cells as well as an
agent for gene transfer and trans-membrane transport [12].
The case of synthesis of carbon nanotubes are considered as one of the
strongest nano materials for considering the pathobiology of the disease
under treatment. The efficient possibility of the nano tubes to target
the cell receptors and blocking the cellular pathway of the disease by
enabling the drug through the cell membrane is however a preferable
system to kill the tumor. The promise of a successful cancer treatment
using gold nano particles have led to bio affinity of gold nano particle
probes for molecular and cellular imaging for early screening of the
cancerous cells [28].
Mesoporous silica nano particles also meet the demand
of cancer therapy by reducing the toxicity issues of many
chemotherapeutic drugs. Due to the highly dynamic and heterogenous
nature of the cancer, they can readily adapt to the stress imposed onto
them. MSN-based nanocomposites target different phenotypes of a tumour
thus holding a promising way to develop a co-operative therapy. FDA has
recently approves a kind of ultrasound multimodal silica
nanoparticles(Cornell dots) against advanced melanoma for even more
specific diagnosis [24].
Besides that, the green method of synthesizing nanoparticles generated
using plant phytochemicals can be also used in the discovery of new
biomarkers and thus forming the basis of new drugs to fight cancer with
refining diagnosis [29].
Conclusion
Nanotechnology covers a lot of domain today and will
cover a lot more in near future. The creation of nanodevices with their
changing form and multiple purposes as in cancer research will help in
understanding the behavior of physiological markers of a disease and
responsiveness of a drug [30-33].
Thus, exploiting the materials at atom and molecular level for the
promising production of new materials controlling their shape and size
at nano scale level has become a matter of potential concern. Also, it
is necessary to envision that green method of synthesis of the base
product of these devices has number of substantial benefits in context
to several parameters including non-toxicity and cost effectiveness.
However, the assessment of nano materials into human body while treating
several disparities, the release of particulate materials into the
disease environment as well as the extent to which they enter the
intended sites of penetration will determine the ultimate risk of
exposure particularly for those that cannot be metabolize by our body.
Therefore, it is worth considering before formulating them into such
scenarios.
Acknowledgement
The authors acknowledge the support from the entire
biotechnology department, Assam down town University,Panikhaiti,
Guwahati, Assam, India.
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