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Nanotechnology in Healthcare: Applications and Challenges

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DOI: 10.4172/2161-0444.1000312

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 Medicinal chemistry Patel et al., Med chem 2015, 5:12
http://dx.doi.org/10.4172/2161-0444.1000312

Review Article Open

Nanotechnology in Healthcare: Applications and Challenges

Suprava Patel*, Rachita Nanda and Sibasish Sahoo
Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Raipur, Chhattisgarh, India

Abstract
In this era of nanoscience, advances of nanotechnology have led to the creation of new generations of nanostructures, each characterized by their explorative
utilization in various types of applications in biomedicine and bio-engineering. These applications are expected to significantly improve the diagnosis and
therapeutic aspects of many diseases. The materials have been explored and reported as components of biosensors and as very efficient drug delivery platform.
Though, few nano-materials have been reported to be used in clinical medicine, but not coherently effective. This could be because of nano-toxicity which is a
potential limitation for its use in biological system. A brief description on the development of nanostructure for biomedical application over the years in terms of
new materials and understanding of their interaction with the body, may lead to better biocompatible nanostructures.

Keywords: Nanotechnology; Health care application; Nanotoxicity; Challenges

Perspectives of Nanotechnology
Introduction Applications in Medicine and Health
Nanotechnology and science of nanomaterials provide apt potential in engineering of
Nanotechnology has potential to remarkably affect the diagnostic and therapeutic
materials and at present is the enormously growing and developing scientific technology.
approach for a disease. The unparallel sensitivity and performance, enhanced
It is defined as the study of controlling, manipulating and creating systems based on their
durability and flexibility, unique physic- chemical properties of nano-materials, have been
atomic or molecular specifications [1]. As stated by the US National Science and
exploited in medical diagnosis (Table 1) for early detection of diseases, in target
Technology Council, the essence of nanotechnology is the ability to manipulate matters at approached clinical therapy (Table 2) and in regenerative medicine for reconstruction of
atomic, molecular and supra-molecular levels for creation of newer structures and devices damaged tissues.
[2]. Generally this science deals with structures sized between 1 to 100 nanometer (nm) in
at least one dimension and involves in modulation and fabrication of nanomaterials and Medical diagnostics
nanodevices. It has been endured as an area of intense scientific research in various fields
like optical, electronic and biomedical fields. Bacterial cells, plant cells and mammalian The entire world has witnessed the phenomenon revolution in biosensors towards
cells which are more than 100 nm size can easily engulf or internalize the particulates of Point-of-care testing by glucometer for blood glucose monitoring. It has developed from
nano-size like viruses (75-100 nm), proteins (5-50 nm), nucleic acids (2 nm width) and very primitive enzyme based method to amperometric based principle and further
atoms (0.1 nm). If we compare a single human hair diameter (50 µm) to 1 nm nanofibre, development of reverse iontophoresis method. The technique has evolved from invasive
hair will be 50,000 times larger than the size of 1 nm [3]. The great visionary late Nobel procedure to non-invasive monitoring, from in-vitro diagnosis to in- vivo monitoring of
Physicist Richard P Feynman first designed the idea of molecular manufacturing in 1959. blood glucose.
The legendary scientist who first suggested that devices and materials could someday
Similarly many nano-devices and nano-biosensors have been innovated to monitor
have atomic specifications and that this development path cannot be avoided [4]. For the bio- molecules, at a very low concentration resulting in detection of disease at an
years this science have engaged scientist in exploring the very unique physico-chemical early stage. They can be a novel and powerful tool for cancer detection system. The
properties of nanoparticles. traditional diagnostic modalities are unable to detect tumors in their initial stage and more
imprecise in differentiating benign from malignant stage. Compared to the conventional
methods, novel nanoparticles (NPs) are capable of yielding selective imaging of affected
areas.

Clinical therapy and drug delivery systems

The innovative NPs not only act as efficient imaging agents for identifying the
diseased tissues but are also ideal carriers to deliver anticancer drugs and other
therapeutic drugs at the target site with optimum proficiency and minimum collateral
damage to the

*Corresponding author: Dr. Suprava Patel, Assistant Professor, Department of Biochemistry, All India Institute of Medical
Sciences (AIIMS), Raipur, Chhattisgarh-492 099, India, Tel: +918518881707; E-mail: [email protected]

Received October 30, 2015; Accepted December 07, 2015; Published December
11, 2015

Citation: Patel S, Nanda R, Sahoo S (2015) Nanotechnology in Healthcare: Applications and Challenges. Med chem 5: 528-
533. doi: 10.4172/2161- 0444.1000312

Copyright: © 2015 Patel S, et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original
author and source are credited.

Figure 1: The diagram depicts the applications of nanotechnology in various research fields. Nanotechnology spans many areas like biotechnology, national security and defense, food and agricu

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Citation: Patel S, Nanda R, Sahoo S (2015) Nanotechnology in Healthcare: Applications and Challenges. Med chem 5: 528-533. doi: 10.4172/2161-
0444.1000312

Nanomaterial Use and its Principle References

Graphene oxide Detect very low level of cancer cells (3-5 cancer cells/ml blood) Yoon et al. [5]

Single-walled Carbon nanotubes (SWNT) Monitor blood nitric oxide level in inflammatory diseases. It uses the principle of Iverson et al. [6]
fluorescent signal

Silver based nanoparticle and Raman dye-labeled DNA hairpin probes Targets specific markers in infections. Uses the principle of SERS (surface –
enhanced Raman Scattering) Wang et al. [7]

Nanoflares (first genetic based approach for detecting cancer Enable live cell detection of intracellular mRNA. It is based on the principle of
cells from blood) fluorescence. Halo et al. [8]

Iron oxide nanoworm particles coated with proteases (matrixmetalloproteases, cathepsins) It can home to a tumor and interact with cancer proteins to produce thousand of Kwong et al. [9]
for early detection of cancer biomarkers which can be detected in patient’s urine by mass spectrometry.

Target specific magnetic nanoparticles It allows real-time monitoring the glioblastoma multiforme microvesicles in blood. The are detected by a miniaturized, hand-held Shao et al. [10]
device.
NanoVelcro chip – anti-EpCAM antibody coated silicon To detect and isolate the circulating tumor cells. It utilizes the principle of laser micro- dissection (LMD).
nanowwires overlaid with polydimethylsiloxane Lu et al. [11]

On-chip separation and detection of biological agents like bacteria and viruses in blood, urine, saliva and food. It uses the
Silver nanorod array substrate Negri et al. [12]
principle of surface enhanced Raman spectroscopy (SERS).

To detect the influenza virus in sample. It is based on the principle of dynamic light
Gold nanoparticles coated with influenza A specific antibodies. scattering (DLS). Driskell et al. [13]

Gold nanoparticles modified with monoclonal anti- For detection of influenza A virus in blood. It utilizes the principle of colorimetric
hemagglutinin antibody (mAb) immunosensing. Liu et al. [14]

Nanoparticles that form clumps To detect presence of cancer biomarker like Prostate specific antigen and viral markers like p24 in low HIV viral load. de la Rica et al. [15]

In-vitro diagnostic test for detecting nanomolar concentration of myelopeoxidase (MPO). It is an economic and fast detecting
μQLIDA (microfabricated Quantum dot-linked immune-
diagnostic assay) immunofluorescence sensor with the capability of 2 μl of analyte solution and detecting nanomolar concentration of MPO or other Yu et al. [16]
analytes.

These are ultra-stable, biocompatible and nontoxic luminescent nanoprobes. It can be an ideal diagnostic tool for long-term
Silicon quantum dots and fluorescent nanodiamonds Montalti et al. [17]
bioimaging and also a non-toxic vector for drug delivery.

Iron-oxide magnetic nanoparticles coated with peptide (poly- dopamine) To locate cancerous cells clusters during Magnetic Resonance Imaging (MRI) and photothermal cancer therapy using near-infrared Wu et al. [18]
laser irradiation.

[18F]-FAC family of positron emission tomography imaging agents Tumors responsive to chemotherapeutic drugs appear as bright images in PET scans. Braas et al. [19]

Nano-MRI agent Bind to a β3-integrin found on the surface of newly developing blood vessels Liu et al. [20]
v

Under FDA approved nanosensor for genetic test for warfarin sensitivity. It allows
Gold nanoparticle based molecular diagnostic platform testing for other genetic targets Lefferts et al. [21]

Table 1: Nanomaterials used in biosensing of analytes for early diagnosis of specific diseases.

Nanomaterial Use and its Principle References

Biomimetic nanosponge For detoxification treatment Hu et al. [23]

For non-invasive ultrasound therapy. It converts light to sound and generate high pressure sound waves to disrupt cells. It is
Nano-composite film of carbon nanotubes (CNTs) Baac et al. [24]
also called ‘Invisible knife for non- invasive therapy.

Gold/Bismuth based nanoparticles To concentrate radiation used in radiation therapy to treat cancer tumors. Cooper et al. [25]

Poly(ethylene oxylated) single-walled carbon nanotubes Maintains brains blood circulation. Alqathami et al. [26]

SWNT functionalized with HER2 antibody For selective destruction of breast cancer cells Bobadilla et al. [27]

GRGDS-NPs (copolymer of poly(lactic-co-glycolic acid) and poly-ε-L-lysin with These are novel hemostatic NPs administered intravenously to activates the clotting process and reduce bleeding due to
Xiao et al. [28]
polyethylene glycol terminated with arginine-glycine-aspartic acid) based targeting ligands trauma.

Fidgetin-like 2 (FL2) small interfering RNA (siRNA) FL2, the regulator of cell migration is targeted by the nanoparticle encapsulated siRNA, to promote wound closure and
nanoparticles Shoffstall et al. [29]
regeneration.
Fullerene nanoparticles Reduce allergic reactions Charafeddine et al. [30]

Carbon nanotube based nanofiber scaffold Cardiac tissue engineering Ryan et al. [31]

The coated nanoscaffolds, stimulates growth and differentiation of cardiomyocytes into functioning cardiac tissue and thus
Thymosin β4 coated poly (ε-caprolactone) nanoscaffolds Oh et al. [32]
have potential for cardiac replacement after any cardiac event.

BIND-014, a prostate specific membrane antigen (PSMA)-

targeted NP containing docetaxel Used in chemotherapy naïve metastatic castrate with refractory solid tumors Kumar et al. [33]

siRNA encapsulated in a cyclodextrin based nanoparticle To inhibit the key enzyme production in cancer cells Mita et al. [34]

Gelatin nanoparticles as acarrier for osteopontin (OPN) Given intranasally for treatment of ischemic stroke Davis et al. [35]

Nanoparticles poly (D,L-Lactitide-co-glycolide)-(PLGA-) based polymer Carrier for insulin delivery in diabetic patients Kanasty et al. [36]

Monodisperse microgels consisting of chitosan matrix, enzyme nanocapsules and The microgels with enzyme nanocapsules monitor insulin release and basal blood sugar level in type 1 diabetes mellitus. Joachim et al. [37]
recombinant human insulin
Nanocrystalline silver Antimicrobial agent for treatment of wounds Verma et al. [38]

Bioreducible polycations-polymer of Polyethylenimine (PEI) pDNA carrier with endosomal escape function Gu et al. [39]

Table 2: Nanomaterials used for clinical therapy in various diseases.

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Citation: Patel S, Nanda R, Sahoo S (2015) Nanotechnology in Healthcare: Applications and Challenges. Med chem 5: 528-533. doi: 10.4172/2161-
0444.1000312

neighboring healthy tissues. The therapeutic modality is now being shifted towards
particle size decreases. Ivask et al. had explained about “size-dependent: biological effects of
intracellular molecular targets rather than the cell itself. Intracellular delivery of such
silver NPs. In his study, silver NPs of <10 nm in comparison to NPs >10 nm, proved to be
gene-encoding DNAs, gene- silencing small interfering RNAs or recombinant proteins
more toxic because of their higher intracellular bioavailability [48].
can be achieved by utilizing biocompatible packing materials. The packaging scaffold
usually used are liposomes or bacterial toxins or viral NPs, but usually they get degraded Shape dependent toxicity has also been reflected in different studies based on carbon
and cleared off early from the circulation or may not reach to the potential target site. nanotubes, nanorods, nanospheres, silicas, copper, gold and many more. In a comparative
Recent developments in bioreducible polymers have gained more attention in as they are study of copper oxide (CuO) nanorods to CuO nanospheres by Kennedy et al. results
amenable to molecular programming through sensors that can respond to the changes in indicated that the higher surface area of nanorods released more ions and therefore more
ion concentrations in the micro- environment and thus can differentiate between toxic [49]. Yet optimizing the synthetic methodology, unique properties may be enhanced
extracellular and intracellular sites [22]. with minimal adverse reactions. Almodarresiyeh et al. in their studies devised a new
methodology to synthesize rod-like zincoxide (ZnO) nanoparticles in presence of
Tissue growth and regenerative medicine polymers (polyethylenimine and hexamethylenetetramine). These NPs of ZnO have a
The potential of nanotechnology extends beyond diagnostics and treatment; it also wide band gap semiconductor with large excitation energy that favors its suitability to be
promises breakthroughs in regenerative medicine. By 2030, scientists will have been used in optoelectronic devices [50-52].
using nanoscale materials to stimulate tissue regeneration. They provide sustained
delivery of bioactive molecules to support survival, infiltration and proliferation of cells
Solubility of NPs in the biological media
for tissue engineering. The expected outcome of such treatment modality is to have The solubility of the nanomaterials in a medium is affected by its particle dispersion
complete tissue replacement and functional recovery. Extracellular matrix formation is and agglomeration state, which in turn is influenced by its size and surface ratio. Thus the
enhanced by using CNT, nanowires and nanoparticles. Biomimetic hydrogels are used as reciprocal action between the particle and its solvent also a determining factor for toxicity
controlled biomolecule delivery of growth factors to expedite bone regeneration [40-42]. of NPs. Hamilton et al. illustrated the greater toxic effect of longer TiO2 nanofibers (15
The nanofilled composites provide better compressibility, tensile strength and flexure mm) in comparison to shorter fibers because the longer fibres are insoluble in lung fluids
strength compared to traditional composite microparticles. Crosslink agent composed of and remain in lungs for longer time which initiates inflammatory response by the alveolar
partially hydrolyzed polyacrylamide (HPAM) and nanocrystalline hydroxyapatite (nHAp) macrophages [53].
can be a novel scaffold for osteochondral repair [43]. Chodritin sulfate nanoparticles
(CSnps) within the scaffold of chitin blended with poly(butylenes succinate) have been Yang et al. reported in his study that silver NPs dissolved in lower ionic strength
used for skin repair in wounds [44]. It provides superior aesthetic sense as it is resulted in greater toxicity than the same NPs in a higher ionic strength [54]. TiO2
biodegradable, biocompatible and forma a porous layer for better nutrient exchange. or ZnO exhibits different diameters in different biological milieu and thus toxicity differs
Polyethylene glycol-based hydrogel scaffold are aid in retention and growth of accordingly.
transplanted heart cells in myocardial infarction [45]. Glass slide coated with garphene
oxide film stimulate the adhesion and osteogenic differentiation of human adipose-derived Surface chemistry (charge/surface coatings)
stem cells [46]. Collagen, chondroitin-6-sulfate, chitosan and laminin matrix, together
Surface charge of a NP is also a major determinant factor for its interaction with the
have been demonstrated to support islet function in- vitro and allow islet survival and
biological environment. As per Dejaguin-Landau- Verwey-Overbeek (DLVO) theory,
post-transplantation vascularization [47]. Systemic understanding of the interaction
stability of particles is determined by the net electrostatic surface interactions of the
between the cells and the in-vivo microenvironment at nanoscale level can abet for better
particles and the Van der Waals forces. As depicted in a study by Stebounova et al.
designing and fabrication of biomimetic scaffolds.
polymer- coated silver NPs with higher surface charge were more stable than the silver
NPs with unspecified coatings in simulated lung fluid [55]. Park et al. suggested that
Toxic Outcomes of Nanostructures negatively charged silica (SiO 2) NPs had more toxic effect compared to weakly negatively
Nanotechnology is now regarded the double edged sword. One edge depicts for charged silica NPs. Articles have revealed significant cellular uptake of positively charged
potential health benefits and the other for potential health risks. Nanotechnology provides SiO2 owing to their enhanced opsonisation by plasma proteins. SiO 2 also induce
numerous advantages such as high performance, reduced size, mass and power intracellular reactive oxygen species (ROS) generations and exert their toxic effect by
consumption, POC testing and improved reliability and robustness. In order to oxidative stress [56].
explore the characteristic physicochemical properties of these nanostructures, the toxicity
aspect is overlooked. They elicit unique and unpredictable biological responses, as Composition and degree of purity
discussed below, because of their tunable properties. Nanomaterials are composed of heavy metals with known toxicity such as Cadmium
Selenide (CdSe) NPs are toxic to rat liver and renal cells [57], carbon based NPs cause
Size, shape and surface area of the nanomaterial lung tumors [58] and iron containing NPs are toxic to nerve cells [59].
Because of their nanoscale size, these particles are easily accessible to the vital cells
Liu et al. in their study provided evidences for genotoxic and cytotoxic effects of
and organs. They interact with the host cell and remain adhered to the surface or
cadmium sulfide (CdS) on renal cells, liver cells, spermatozoon and tested organs [57].
internalize by translocation or by receptor mediated endocytosis. Intracellularly also they
may alter the cellular metabolism by interacting with the subcellular organelles. The Harper et al. assessed the impact of synthesis method and purity on the
surface area ‘o’ the particle increases with decrease in particle size and the ratio of surface biocompatibility of peptide-capped gold-glutathione (Au-GSH) NPs. The study displayed
to total atoms or molecules increases exponentially as the significant morbidity and mortality for Au- GSH-(Trp)2 purified by dialysis. The toxic
effects were also significant

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Citation: Patel S, Nanda R, Sahoo S (2015) Nanotechnology in Healthcare: Applications and Challenges. Med chem 5: 528-533. doi: 10.4172/2161-
0444.1000312

for Au-GSH-(His)2 synthesized by either dialysis or ultracentrifugation whereas Au-GSH-

(Met)2 manifested least toxicity. A prudent synthesis protocol can yield high degree purity Lack of uniformity of toxicity
for NPs and show improved biocompatibility [60]. Nanomaterials of different composition, size or shape may be toxic to a different set
of cells at different set of exposure conditions. The target cell and the target moieties for
Aspect ratio dependent toxicity toxicity varies with the composition, size, shape, charge, aggregation, coating and
It is seen that toxicity is directly proportional to the aspect ratio (ratio of highest to solubility of nanoparticles. CNTs at 400 µg/ml are cytotoxic to human T-cells, 3.06
the lowest dimension considered the particles are of similar size). NPs with high aspect µg/cm2 on alveolar macrophages whereas cell cultures exposed to 3.8 µg/ml do not reveal
ratio include nanotubes, nanowires and nanorods whereas low aspect ratio seen in any cytotoxicity [22].
spherical, oval, cubic forms [61]. Asbestos fibers longer than 10 microns cause lung
cancer, those of 5 micron size lead to mesothelioma in lungs whereas fibers of 2 Lack of standardization in model systems and test assay
microns with asbestosis. The longer asbestos fibers are degraded perpendicularly and There is no good in vivo model to elucidate the physical, chemical and biological
made shorter and cleared by the macrophages. Smaller fibers are cut longitudinally behavior precisely. It is difficult to validate the results of interplay of NPs with cells as the
generating more of smaller diameter fibres which are more difficult to be removed. outcome varied with different set of cells even if the test assay conditions remain same.
However slow clearance of degraded particles would lead to accumulation of the longer
fibers in the alveoli inducing inflammatory changes. Long aspect ratio of SWCNT has been Lack of standard synthesis protocol
signoificantly associated with pulmonary toxicity when compared to the spherical
amorphous carbon black particles [62]. Production of nanomaterials utilizes numerous synthetic reagents which are also
toxic. Efficient synthetic pathway must be developed with avoidance to use of precarious
Aggregation state of NPs pollutants. Prudent use of synthetic material and comply with safety guidelines can ensure
for yield of high purity and better biocompatible nanoparticle.
Aggregation is an ubiquitous phenomenon among all NPs and mediate cellular
uptake of bio-molecules. Albanese et al. investigated uptake of transferrin-coated gold NP Lack of efficient analytical tools
aggregate on different cell lines. The aggregates reduced the uptake via receptor-
mediated- endocytosis in HeLa and A549 cells. In contrast, foe MDA-MB-435 cells, the Nanotechnology deals with nanoscale structures, hence novel analytical methods
aggregates internalized independent of transferring receptor via unknown mechanism. The need to be developed to acquire the nanomaterial description precisely such as particle
study predicted that NP aggregate bring about multiple cellular responses [63]. Tripathy et size, surface charge, surface chemistry, crystalline state, aggregation state and its
al. demonstrated about the effects of particle size and aggregation of ZnO nanoparticles. distribution. New innovations in metrological technology requisite to predict the behavior
Smaller aggregates tend to have higher dissolution rate and cellular uptake resulting in ROS of nanoparticle in biological media.
generation and induction of cellular apoptosis [64].
Lack of understanding of impact on biological system
Antigenicity of NPs
Impact on health and safety issues still unclear in terms of cellular or organ toxicity,
Nanoparticles can be antigenic themselves and the immunogenicity depends on their genotoxic or carcinogenic. These materials are small enough to be inhaled and the
physicochemical properties. They can be opsonized by plasma proteins and result in particles accumulate in lung alveoli to induce inflammatory changes or carcinogenic
activation of complement cascade. As reported by Trynda-Limiesz et al. nab-paclitaxel effect. This would be of prime concern because the workers will be under threat of
in pigs evoked immunological type of response when compared to albumin control [65]. occupational hazard.
Abrams et al. documented that liposomal siRNA delivery vehicle LNP201 induced
cytokine release (cytokine storm) typical of unregulated innate immune response [66]. Lack of in-vivo monitoring systems
Substantial infrastructure for in-vivo analysis of the nanomedicines, inability to
Challenges for Nanotechnology monitor multiple probes and patients need to be admitted for analysis, are the major
Although nanotechnology is a very rapidly growing field, still the product availability factors that preclude optimization of the biological activities.
is far away from reach because of various hurdles at different stages of development. The
barriers for growth, as enumerated below, if overcome can bring about revolutionary Lack of standardized safety guidelines
changes in the field of health care and medicine. Due to complex nature of nanomedicines and their multiform toxicity, it is difficult
to outline a particular safety guideline for a particular nanoparticle. To provide a safety
Lack of knowledge NP components and their characteristics
protocol, empirical evidence and extensive pre-clinical testing is mandatory.
There are numerous varieties of nanostructures, with different compositions and
actions. The in-vitro and in-vivo physicochemical phenomenon of these NPs are not well Lack of well trained workforce
understood. Hence identifying the right nanomaterial for the intended indication is crucial. High energy consumption due to which production cost is very high and restricted
PEI is being recognized as an excellent cargo for intracellular nucleic acid targeting.
accessibility to people. This is a major hindrance for the goal to be achieved for POC
Nonetheless, it is also regarded as a significant cytotoxic agent. Owing to its higher
testing to the remote areas.
proficiency in drug delivery, methods have been devised to reduce its toxicity by
crosslinking low molecular weight PEI to dithiodipropionic acid di(N-succinimidyl ester) It is the need of the hour to ensue towards efficient production of nanostructures
[22]. ‘Safe by Design’, through green chemistry, optimizing standard protocols for synthesis,
production and clinical testing. In shaping of ‘Green Nanotechnology’, contribution and
involution of scientific personnels, persons from governmental sector, industrial and
workforce representatives is required in order to modulate the

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0444.1000312

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Citation: Patel S, Nanda R, Sahoo S (2015) Nanotechnology in Healthcare:

Applications and Challenges. Med chem 5: 528-533. doi: 10.4172/2161-
0444.1000312

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