Applications of nanoscience in photomedicine

550 Pages·2015·125.21 MB·English

by  Avci, Pinar, Hamblin, Michael R.

1
Introduction
M. R. Hamblin and P. Avci,
Harvard Medical School, Boston, USA
DOI: 10.1533/9781908818782.1
Abstract: We summarize the historical development of nanotechnology
over the last 55 years, and of photomedicine over the preceding 3000
years. The rationale for the fundamental connection between
nanoscience and photomedicine lies in consideration of the dimensions
of the wavelength of light. Since visible wavelengths are of the order of
hundreds of nanometers, it follows that particles in the nanosized
domain will be best placed to interact with light, via absorption,
scattering or plasmon resonance. This type of interaction has a natural
affinity to the new field of theranostics where multifunctionality is
highly encouraged. Chapters in the present book can broadly be
divided into two groupings. First we have disease imaging and tissue
analysis applications that rely on the creative use of both light and
nanomaterials. Secondly we have a group of chapters concentrating on
the therapeutic effects of light (frequently pulsed lasers) in combination
with various kinds of nanoparticles.
Key words: History of nanotechnology; history of photomedicine;
fullerenes; quantum dots; optical imaging, nanoparticles; theranostics.
The discipline now known as nanotechnology is accepted to have
originated in December 1959 when US physicist Richard P Feynman gave
a speech at an American Physical Society meeting at the California
Institute of Technology, entitled There’s­Plenty­of­Room­at­the­Bottom
[1]. Feynman argued that if machines could be constructed to manufacture
objects at the atomic scale capable of storing information “all of the
information that man has carefully accumulated in all the books in the
world could be written in a cube of material one two- hundredths of an
© Elsevier Limited, 2015
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Applications of Nanoscience in Photomedicine
inch wide – about the size of the smallest piece of dust visible to the
human eye.” He also suggested that at the nano-s cale the physical
properties of matter would change in importance such that mass would
become less important, while surface phenomena would begin to
dominate behavior.
In 1974, Norio Taniguchi first used the word “nanotechnology” [2], to
describe an ion sputter machine that could enable a “production
technology to get extra- high accuracy and ultra- fine dimensions, i.e. the
preciseness and fineness of the order of one nanometer.” In the 1980s,
Eric Drexler wrote the first book on nanotechnology, Engines­of­Creation
[3] in which the concept of molecular manufacturing was introduced. It
is largely due to Drexler that the potential of nanotechnology and
nanomanufacturing has fired the public’s imagination. In 1985, fullerenes,
or “buckyballs”, were discovered [4], although the structure had been
predicted 15 years previously [5] by RW Henson [6]. C60 was named
“molecule of the year” in 1991 [7], and led to the editorial entitled A­
wide­open­playing­field­for­chemists [8]. Quantum dots were discovered
in the early 1980s and Louis Brus from Columbia received the first Kavli
Prize in Nanoscience in 2008 for his pioneering efforts in this field [9].
Originally called “semiconductor nanocrystals” the term “quantum
dots” was first used by Reed et al. in 1988 [10]. Multi- walled carbon
nanotubes were discovered by Iijima in 1991 [11] and the single-w alled
variety in 1993 by Bethune and colleagues of the IBM Almaden Research
Center in California [12].
By the 1990s, nanotechnology was advancing rapidly. In 1990, the first
academic nanotechnology journal was published [13], in 1993 the first
Feynman Prize was awarded by the Foresight Institute to Charles
Musgrave “for his work on modeling a hydrogen abstraction tool useful
in nanotechnology” [14], and by 2000 President Clinton announced the
foundation of the US National Nanotechnology Initiative (NNI) [15].
The NNI proposed the development of nano- enabled tools to address
many current challenges facing the USA and the rest of the world,
including: clean, affordable energy; stronger, lighter materials; very- low-
energy lighting; biosensors to monitor human functions and to detect
external threats; novel techniques to clean up the environment; smart
drug delivery vehicles with fewer side effects; theranostic drugs with
multifunctional capability to both detect and treat disease.
Photomedicine is defined as the study of diseases caused by light and the
use of light to detect, diagnose and treat disease [16]. Photomedicine did not
have such a well- defined origin as did nanotechnology. Ancient Egyptians
and Persians treated skin diseases by consuming various plants and exposing
2
Introduction
themselves to sunlight. In 1890 the role of sunlight in protecting children
from rickets was discovered [17]. The modern era of photomedicine dates
from the turn of the twentieth century when photodynamic therapy was
discovered in Munich [18–20] and Nils Finsen in Denmark won the Nobel
Prize for Medicine in 1904 for treating cutaneous tuberculosis with
phototherapy [21]. Heliotherapy enjoyed a period of popularity in the first
half of the twentieth century with numerous clinics constructed in the Alps
to expose patients suffering from a variety of diseases to sunlight [22]. The
scientific study of low- level laser therapy and photodynamic therapy both
began in the 1970s and both continue to be investigated at increased levels
to the present day. Optical imaging and the application of biomedical optics
to diagnose disease probably came to prominence with the discovery of
optical coherence tomography in the 1990s [23] although there had been a
variety of fluorescence and other simple optical imaging techniques being
sporadically explored for many years earlier. Now there are many
sophisticated optical methodologies being studied and explored, including:
in­vivo confocal microscopy [24], optical frequency domain imaging [25],
diffuse optical imaging [26], fluorescence tomography [27], Brillouin
microscopy [28], Cerenkov imaging [29], polarization- sensitive techniques
[30], photoacoustic techniques [31].
It has long been observed that many (if not most) medical applications
of nanotechnology involve light at some level. Often this is the relatively
simple use of dynamic light scattering to characterize the size and shape
of nanoparticles or the use of confocal fluorescence microscopy to
visualize the uptake and localization of nanoparticles within cells.
However, many nanomedicine applications also involve light at a much
more fundamental level. Here the remarkable similarity of scale between
the size of the nanoparticles and the wavelength (100s of nanometers) is
crucial. Plasmon resonance [32], tailorable absorption spectra of gold
nanorods and nanoparticles [33], and the tunable optical properties of
quantum dots are good examples of the relationship between the size of
the nanostructure and the wavelength of light giving added functionality
or more versatility to the nanoconstructs. Furthermore it is obvious that
most optical interactions take place at the surface of materials due to the
difficulty that light faces in penetrating nontransparent substances.
Therefore since one of the most important properties of nanomaterials is
the fact that the surface area to mass ratio is maximized, the strength of
the light- matter interaction is expected to be much more pronounced in
nanoscale forms of matter than in macroscopic matter.
The present textbook has been divided into two broad sections. The
first section concerns technologies for laboratory investigation, imaging
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Applications of Nanoscience in Photomedicine
and novel diagnostics and the second section concerns experimental
therapeutics.
In chapter 2, McLeod and Ozcan describe an imaging system broadly
based on a smart- phone that can image nanoparticles and viruses with
wide- field capability and high- sensitivity and resolution. Chapter 3 by Kim
and co- workers covers the use of molecular photoacoustic imaging with
nanoparticle contrast agents to image tumors; a technique that may also be
dual modality when combined with ultrasound. Mittal and Potma describe
in chapter 4 how multi- photon microscopy techniques using nonlinear
optics and pump- probe spectroscopy can allow chemical imaging of
biomolecules involved in various diseases and in drug delivery. In chapter
5, Laurent Bentolila covers the use of photoluminescent quantum dots and
their biological applications in cancer diagnosis and imaging. Hleb and
Lapotko describe in chapter 6 how plasmonic nanobubbles can be used as
multifunctional theranostic agents applied to tumors such as prostate and
head and neck cancer. Chapter 7 by Cheng and colleagues covers the use
of near- infrared fluorescent nanoparticles, some of which may be enzyme-
activated and which may play a role in multimodality imaging of cancer.
In chapter 8, Sun and Fan describe the basic techniques of optofluidics
where light is used to move, manipulate, probe and measure nanoparticles,
nucleic acids, and other biomolecules under flow conditions. Lo and co-
workers (chapter 9) cover the design of lab- on-a- chip devices making use
of the properties of light and microfluidics together (optofluidics) for
applications in cancer, hematology, and genetics. In chapter 10, Seifalian
and colleagues review the “hot topic” of optogenetics where photoactive
channel- rhodopsins can be inserted into the brain via targeted virus
delivery to switch on certain neural pathways when activated by light.
Mohanty in chapter 11 covers neurophotonics at the nanoscale, focusing
on optical tweezers and beacons, photonic control of axonal guidance,
localized and patterned optical stimulation, two-p hoton optogenetics,
and optical recording of neuronal activity.
The first chapter (chapter 12) in the second section is by Kah et al. who
discuss the applications of gold nanorods in photothermal and
photodynamic cancer therapy, targeting and sensing, imaging, and
diagnostics and in smart- release drug delivery. Singh and associates in
chapter 13 discuss differently shaped gold nanoparticles with a focus on
antibody and nanobody- targeting applied to drug delivery, cancer and
arthritis. Melancon and co- workers in chapter 14 discuss the application
of targeted gold nanoshells functionalized with aptamers, antibodies, and
peptides in light-a ctivated cancer therapy and drug-d elivery. Chapter 15
by Panchapakesan and others covers the use of carbon- based nanoparticles
4
Introduction
such as graphene and carbon nanotubes for photothermal therapy used
for gene and macromolecular delivery, and for tumor targeting. In chapter
16, Meunier and colleagues introduce the concept of “nano- opto-
transfection”, which uses light-a ctivated plasmonic gold nanoparticles,
carbon nanotubes, and polymeric nanolenses to porate cells allowing
introduction of nucleic acids. Lim and Austin discuss in chapter 17 how
rare earth upconverting nanoparticles can potentiate photodynamic
therapy via a nonsimultaneous two-p hoton absorption process. In
chapter 18, Barhoumi and Kohane show how light- triggered drug
delivery may operate using photocleavable, photo- oxidizable, and
photopolymerizable liposomes and micelles. Perni and Prokopovich in
chapter 19 switch gears and show how light-a ctivated nanoparticles with
different kinds of photosensitizer-a ttachment strategies can inactivate
drug- resistant pathogenic microorganisms. Nonell and co- workers in
chapter 20 cover the use of silica nanoparticles to act as sunscreens, to
deliver enzymatic and flavonoid anti- oxidants and to potentiate
photodynamic therapy using methylene blue and porphyrins. In chapter
21, Frochot et al. cover another application of silicon nanoparticles –
concentrating on targeting and preparation of multifunctional theranostic
agents with magnetic resonance, fluorescence and photodynamic
capabilities. In chapter 22, St Denis and Hamblin cover a wide range of
supramolecular nanoparticle- based platforms to deliver different
photosenitizer structures. Hasan and colleagues in chapter 23 cover the
design of “smart” photoactive liposomal structures that can be actively
or passively targeted, and whose release can be triggered by light, heat or
pH and by receptor recognition. In the last chapter Zheng and associates
describe a novel concept called “porphysomes”, in which lipid- porphyrin
conjugates self- assemble into highly quenched nanoparticles that can be
photothermally activated, but when they are unquenched in cells they
become highly fluorescent and photodynamically active.
References
1. Feynman, R.P. (1960) There’s plenty of room at the bottom. Engin­Sci
22–36.
2. Taniguchi, N. (1974) On the basic concept of “nano-technology”. Proc­
Intl­Conf­Prod­Eng­Tokyo, Japan Society of Precision Engineering, Part II
(1974).
3. Drexler, K.E. (1986) Engines­ of­ Creation:­ The­ Coming­ Era­ of­
Nanotechnology. Garden City, NY: Doubleday.
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Applications of Nanoscience in Photomedicine
4. Curl, R.F., et al. (2001) How the news that we were not the first to conceive
of soccer ball C60 got to us. J­Mol­Graph­Model 19: 185–6.
5. Baggott, J. (1994) Perfect­ Symmetry­ –­ The­ Accidental­ Discovery­ of­
Buckminsterfullerene. Oxford, UK: Oxford University Press.
6. Thrower, P.A. (1999) Editorial. Carbon 37: 1677.
7. Koshland, D.E., Jr. (1991) Molecule of the year. Science 254: 1705.
8. Culotta, L. and Koshland, D.E., Jr. (1991) Buckyballs: wide open playing
field for chemists. Science 254: 1706–9.
9. Brus, L.E. Kavli­Prize­Lecture:­Semiconductor­Nanocrystals. Available
from: http://go.nature.com/jI95ft, 2008.
10. Reed, M.A., et al. (1988) Observation of discrete electronic states in a zero-
dimensional semiconductor nanostructure. Phys­Rev­Lett 60: 535–7.
11. Iijima, S. (1991) Helical microtubules of graphitic carbon. Nature 354:
56–8.
12. Bethune, D.S., et al. (1993) Cobalt-c atalysed growth of carbon nanotubes
with single- atomic-layer walls. Nature 363: 605–7.
13. Bate, R.T. (1990) Nanoelectronics. Nanotechnology 1: 1–7.
14. Foresight-Institute First Feynman Prize in Nanotechnology Awarded.
Available from: http://www.foresight.org/Updates/Update17/Update17.1.
html#FirstAwarded, 1993.
15. Roco, M.C. (2003) Nanotechnology: convergence with modern biology
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16. Hamblin, M.R., and Huang, Y.Y. (2013) Handbook­of­Photomedicine.
Boca Raton, FL: CRC Press.
17. Chesney, R.W. (2012) Theobald palm and his remarkable observation: how
the sunshine vitamin came to be recognized. Nutrients 4: 42–51.
18. Raab, O. (1900) Uber die Wirkung fluoreszierender Stoffe auf Infusorien.
Z­Biol 39: 524–46.
19. Jesionek, A., and von Tappenier, H. (1903) Therapeutische Versuche mit
fluoreszierenden Stoffen. Muench­Med­Wochneshr 47: 2042–4.
20. Von Tappeiner, H., and Jodlbauer, A. (1904) Uber Wirkung der
photodynamischen (fluorieszierenden) Stoffe auf Protozoan und Enzyme.
Dtsch­Arch­Klin­Med 80: 427–87.
21. Finsen, N.R. (1967) Nobel­Lectures,­Physiology­or­Medicine­1901–1921.
Amsterdam: Elsevier Publishing Company.
22. Rollier, A. (1923) Heliotherapy. London: Oxford Medical Publishers.
23. Huang, D., et al. (1991) Optical coherence tomography. Science 254:
1178–81.
24. Villringer, A., et al. (1989) Confocal laser microscopy to study
microcirculation on the rat brain surface in vivo. Brain­Res 504: 159–60.
25. Pogue, B.W., et al. (1995) Initial assessment of a simple system for frequency
domain diffuse optical tomography. Phys­Med­Biol 40: 1709–29.
26. Pogue, B., et al. (1999) Comparison of imaging geometries for diffuse
optical tomography of tissue. Opt­Express 4: 270–86.
27. Graves, E.E., et al. (2003) A submillimeter resolution fluorescence molecular
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28. Scarcelli, G., and Yun, S.H. (2012) In vivo Brillouin optical microscopy of
the human eye. Opt­Express 20: 9197–202.
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Introduction
29. Li, C., Mitchell, G.S., and Cherry, S.R. (2010) Cerenkov luminescence
tomography for small- animal imaging. Opt­Lett 35: 1109–11.
30. de Boer, J.F., et al. (1997) Two- dimensional birefringence imaging in
biological tissue by polarization- sensitive optical coherence tomography.
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31. Li, C., and Wang, L.V. (2009) Photoacoustic tomography and sensing in
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wavelength- tunable, gold nanoparticle based optothermal nanoconvertors.
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2
Wide- field nano- scale imaging
on a chip
E. McLeod and A. Ozcan, University of
California, Los Angeles, USA
DOI: 10.1533/9781908818782.9
Abstract: Wide- field imaging facilitates the detection of rare events
and reduces imaging time for large-a rea samples. Nano- scale
imaging enables the detection and enumeration of individual
nanoparticles and sub- cellular bioparticles. Uniting these two
capabilities in a compact and field-p ortable on- chip imaging
platform through lensfree holographic microscopy provides deep
submicron resolution with high sensitivity over fields of view in the
range 10–1800 mm2 – approximately 150–2700 times larger than a
typical 40 × objective field of view. High resolution is achieved via a
pixel super- resolution approach, while high sensitivity is obtained
via a sample preparation procedure that generates self-a ssembled
nanolenses around individual nanoparticles and viruses. The
foundations of these computational imaging approaches, along with
their methodology and results, are discussed.
Key words: computational imaging, digital holography, Fourier
optics, lensfree imaging, on-c hip imaging, nanolenses, nanoscopy,
self- assembly, wide- field microscopy.
2.1 Introduction
Wide- field imaging is highly advantageous in science and engineering,
and in particular, for biomedical applications. It enables researchers and
technicians to detect and identify rare events in sparsely populated
© Elsevier Limited, 2015
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Applications of Nanoscience in Photomedicine
samples, such as potentially cancerous cells in pathology samples,1,2 or
blood cells in whole blood samples.3 Wide- field imaging also enables the
acquisition of statistically significant data from stochastic processes
occurring in large populations, for example, the identification of different
types of micro- scale motion of spermatozoa out of many thousands of
individual sperm.4,5 In static samples that could be imaged with multiple
frames and mechanical scanning using a conventional microscope,
wide- field imaging can significantly reduce image acquisition time
and cost. In the various techniques discussed within this chapter, it is
possible to achieve resolution better than conventional 40 × microscope
objectives, but over fields of view (FOVs) at least several hundred times
larger. Wide- field imaging can also be integrated with active manipulation
techniques, such as opto- electronic tweezers, to select and move specific
objects over long distances.6
Nano- scale imaging is becoming increasingly important in biomedicine
and various other fields. The identification and monitoring of sub-c ellular
elements requires the ability to detect and/or resolve objects with length
scales < 100 nm. These objects may be the biological particles themselves,
such as sub- micron bacteria or viruses, or they may be functionalized
metallic nanoparticles used as labels.7,8 However, optical imaging at
length scales below approximately one-h alf the wavelength is particularly
challenging because of the conventional “diffraction limit”. To overcome
this limit, many different approaches have been developed over the past
several years, including near-fi eld optical microscopy,9–11 photo- activated
localization microscopy,12 stochastic optical reconstruction microscopy,13
stimulated emission–depletion microscopy,14,15 structured illumination,16,17
and interferometric cross- polarization microscopy.18 These approaches
typically require costly and bulky equipment to implement. Furthermore,
they in general use high numerical aperture (NA) objective lenses that
provide high resolution, but with the trade- off of a greatly reduced FOV.
This space–bandwidth trade- off is a fundamental challenge in optical
microscopy.
This chapter discusses recent progress in the union of wide- field and
nano- scale imaging, a feat that is made possible by bypassing objective
lenses or other bulky optical components entirely and imaging a sample
placed in close proximity to an opto- electronic sensor- array such as a
complementary metal- oxide-semiconductor (CMOS) or charge-c oupled
device (CCD) sensor chip. Additionally, on-c hip imaging is synergistic
with portable lab- on-a- chip microfluidic technology. In these devices, in­
situ multiplexed analysis of small analyte volumes is possible in
inexpensive platforms, whose total cost has been significantly reduced by
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Wide-field nano-scale imaging on a chip
mass production of CMOS sensors for consumer electronics (especially
cell phones) and the development of soft- lithography microfluidic
fabrication methods.
2.2 Initial lower- resolution wide- field
imaging approaches
Early on- chip imaging approaches did not provide high- resolution or
nano- scale sensitivity. In these studies, the sample of interest was placed
in close proximity to the image sensor, and object shadows were directly
recorded on the sensor. Because of diffraction and the lack of any lenses,
these objects exhibited significant defocus.19,20 However, due to the very
small object–sensor separation, the resulting images were nonetheless
useful for applications that did not require high-r esolution, such as
cytometry. Pattern- matching approaches could be used to identify and
localize different types of objects.19 In these approaches, typical FOVs
are > 20 mm2.
Fluorescent imaging has also been performed in wide- field on- chip
platforms.21–23 In these studies, an emission filter is typically placed
in the short space between the sample and the sensor, which further
exacerbates defocus. Deconvolution was initially used to counteract
diffraction.22 As an improvement over deconvolution, compressive
decoding methods can also be employed, which improves resolution to
c.10 μm23,24 across a FOV > 200 mm2. Some common misconceptions
about such compressive decoding approaches, which unfortunately
appear in refereed journals, include (1) a misunderstanding that the
fluorescent objects need to be sparse for these approaches to work, which
in fact is not needed because any practical labeled specimen can be
represented as a sparse matrix in, for example, wavelet domain; (2) a
misleading interpretation that the full-w idth-at- half-maximum value
of the fluorescent emission that is sampled at the detector array determines
the resolution in computational fluorescent imaging; just on the contrary
the spreading of the fluorescent emission across many pixels (each with a
decent signal- to-noise ratio) is the route to sub-p ixel imaging performance
under unit magnification fluorescent on- chip imaging (see ref. 24 for
details on this important discussion and its experimental verification).
Recently, a similar level of resolution was also achieved natively (i.e.
without computational methods) across a FOV > 20 mm2 by integrating
high- quality filters into the sensor itself, thus significantly reducing the
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