bionanomedicine: a nanotechnology platform for the 21st century

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Editorial 10.1586/14737159.5.6.839 © 2005 Future Drugs Ltd ISSN 1473-7159 839 BioNanoMedicine: a nanotechnology platform for the 21st century ‘Nanotechnology has the potential to have a revolutionary impact on cancer diagnosis through noninvasive methods and therapy.’ Krishnarao Appasani GeneExpression Systems, Inc., PO Box 540170, Waltham, Massachusetts 02454–0170, USA Tel.: +1 781 891 8181 Fax: +1 781 891 8234 [email protected] Expert Rev. Mol. Diagn. 5(6), 839–840 (2005) The nanoscience and -technology community has recently made tremendous advances across the research and development spectrum. The applications of nanotechnology in biology and medicine are collectively referred as BioNano- Medicine. This new field offers considerable potential for multidisciplinary research and work at the interface of materials, physics, chemistry, biology and medicine. Potential medical applications of this new field include tissue engineering, diagnostics, drug delivery and imaging. Semiconductor-based nanoparticles, known as quantum dots, can fluoresce in different colors, respond to magnetic fields and inter- act efficiently with biologic molecules. Some of these quantum dots are commercially avail- able, while others are undergoing clinical trials. Semiconductor nanocrystals (or quan- tum dots) have many potential biologic and biomedical applications, including imaging of whole animals, individual organs, tissues, cells and receptors, and studying the events occurring within single cells. Some of the applications of nanoparticles or related mole- cules in various fields are briefly described in this review. Bioimaging & diagnosis Molecules that exist in nanospace (in the range of 100 to 0.1 nm), such as quantum dots, were first reported for biologic labeling [1,2]. Since then, these molecules were success- fully used in imaging, as well as to map proteins and genes within human tissue. Recently, it has been demonstrated that near- infrared Type II quantum dots were used in major cancer surgery and for sentinel lymph node mapping in animal studies [3]. Other studies also indicated that nano-sized carbo- hydrate-like materials could be coupled with biodegradable polymers so that they will show easy solubility and biodistribution. Tumor-killing drugs (such as paclitaxel) that could be bound to albumin nanoparticles will provide less toxicity and allow delivery of higher doses during the treatment of advanced cancers. A quantum dot not only reveals the presence of tumor cells in a tissue, but also indicates the behavior of these cells, which helps physicians to prescribe appropri- ate treatment modalities. One caution that must be kept in mind is that most of these quantum dots are derived from cadmium metals, which have some toxic effect on bio- logic tissues and, therefore, optimization studies are needed prior to testing in people. Nanodiscs & nanowire sensors for drug discovery In the drug discovery industry, it is widely known that several diseases could be control- led by developing targets to a set of mem- brane-bound gatekeeper proteins (G-protein- coupled receptors [GPCRs]). Tiny lipid-based nanodiscs were created and GPCRs were sus- pended inside them, and the proteins were tracked as they relayed their chemical signals across the fatty membranes [4]. These nano- discs could shed light on the biochemical For reprint orders, please contact [email protected]

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Page 1: BioNanoMedicine: a nanotechnology platform for the 21st century

Editorial

10.1586/14737159.5.6.839 © 2005 Future Drugs Ltd ISSN 1473-7159 839

BioNanoMedicine: a nanotechnology platform for the 21st century‘Nanotechnology has the potential to have a revolutionary impact on cancer diagnosis through noninvasive methods and therapy.’

Krishnarao AppasaniGeneExpression Systems, Inc., PO Box 540170, Waltham, Massachusetts 02454–0170, USATel.: +1 781 891 8181Fax: +1 781 891 [email protected]

Expert Rev. Mol. Diagn. 5(6), 839–840 (2005)

The nanoscience and -technology communityhas recently made tremendous advances acrossthe research and development spectrum. Theapplications of nanotechnology in biology andmedicine are collectively referred as BioNano-Medicine. This new field offers considerablepotential for multidisciplinary research andwork at the interface of materials, physics,chemistry, biology and medicine. Potentialmedical applications of this new field includetissue engineering, diagnostics, drug deliveryand imaging.

Semiconductor-based nanoparticles, knownas quantum dots, can fluoresce in differentcolors, respond to magnetic fields and inter-act efficiently with biologic molecules. Someof these quantum dots are commercially avail-able, while others are undergoing clinicaltrials. Semiconductor nanocrystals (or quan-tum dots) have many potential biologic andbiomedical applications, including imaging ofwhole animals, individual organs, tissues,cells and receptors, and studying the eventsoccurring within single cells. Some of theapplications of nanoparticles or related mole-cules in various fields are briefly described inthis review.

Bioimaging & diagnosisMolecules that exist in nanospace (in therange of 100 to 0.1 nm), such as quantumdots, were first reported for biologic labeling[1,2]. Since then, these molecules were success-fully used in imaging, as well as to mapproteins and genes within human tissue.

Recently, it has been demonstrated that near-infrared Type II quantum dots were used inmajor cancer surgery and for sentinel lymphnode mapping in animal studies [3]. Otherstudies also indicated that nano-sized carbo-hydrate-like materials could be coupled withbiodegradable polymers so that they willshow easy solubility and biodistribution.Tumor-killing drugs (such as paclitaxel) thatcould be bound to albumin nanoparticles willprovide less toxicity and allow delivery ofhigher doses during the treatment ofadvanced cancers. A quantum dot not onlyreveals the presence of tumor cells in a tissue,but also indicates the behavior of these cells,which helps physicians to prescribe appropri-ate treatment modalities. One caution thatmust be kept in mind is that most of thesequantum dots are derived from cadmiummetals, which have some toxic effect on bio-logic tissues and, therefore, optimizationstudies are needed prior to testing in people.

Nanodiscs & nanowire sensors for drug discoveryIn the drug discovery industry, it is widelyknown that several diseases could be control-led by developing targets to a set of mem-brane-bound gatekeeper proteins (G-protein-coupled receptors [GPCRs]). Tiny lipid-basednanodiscs were created and GPCRs were sus-pended inside them, and the proteins weretracked as they relayed their chemical signalsacross the fatty membranes [4]. These nano-discs could shed light on the biochemical

For reprint orders, please contact [email protected]

Page 2: BioNanoMedicine: a nanotechnology platform for the 21st century

Appasani

840 Expert Rev. Mol. Diagn. 5(6), (2005)

behavior of a host of membrane proteins that have escapeddetailed understanding, and will enable the crystallization ofdifficult membrane proteins.

Lieber and colleagues from Harvard University reportednanowires that allowed them to detect proteins sensitive to thefemtomolar (10-15 M) range [5]. Recently, this group alsodemonstrated the large-scale, label-free, real-time multiplexedelectrical detection of proteins and viruses by silicon nanowirearrays [PERS. COMMUN.]. The integrated nanowire sensor arraysopen up substantial opportunities for diagnosis and treatmentof diseases and fundamental biophysical studies.

Nanofibers for in vivo biologyTechnologies to assess the molecular targets of biomolecules inliving cells were lacking, but are now possible with the use ofnanotechnology. Using self-assembling nanofibers, it is possibleto selectively differentiate the neural progenitor cells and quan-titate cell migration [6]. In addition, nanofibers strongly pro-mote the growth of new blood vessels, both in cell culture andpreliminary animal tests. Synthetic nanofibrous oligopeptidehydrogels, which self-assemble into β-sheet nanofibers, havebeen used in cell culture. Nanofibers can be used to create syn-thetic 3D scaffolds for cell growth and tissue engineering.Angiogenesis-promoting nanofibers may one day help restorehealthy function in patients who have had heart attacks, andeven create a new blood supply for a wide range of engineeredtissues. Although all these discoveries shed light on regenerativemedicine, the biggest challenge is still to engineer a matrix thatgives the cells the right signals.

Nanobarcodes in biodefenseTo take advantage of the nanotechnology, it should be directedagainst diseases such as malaria, HIV and tuberculosis, prima-rily to diagnose the disease at an early stage. Recently, Luo andcolleagues from Cornell University synthesized dendrimer-likeDNA-based nanobarcode technology, and detected severalpathogen DNAs at high sensitivity [7]. This opens a new avenue

in the diagnosis of infectious diseases. The ultimate goal of thisapproach is to create hand-held point-of-use sensors that coulddetect toxins, microorganisms or metabolites, which will have agreat impact in the field of biodefense.

Nanoparticles for drug deliveryUsing modified silica nanoparticles, scientists have deliveredgenes in vivo into the brains of mice. In addition, nanoparticleswere also used in the delivery of small interfering RNA mole-cules. The successful collaboration between industry researchersand clinicians will help us understand the clinical environmentand push the products ahead into the marketplace.

In the context of nanotechnology and diagnosis, there arethree interesting articles in this journal. Jain nicely summarizeshow nanoscale probes would be helpful to analyze receptors andpores in living cells [8]. In addition, this article also summarizeshow nanotechnology will help to reduce the sample volumesand routine diagnostics. Roa and colleagues overview the appli-cations of prenatal genetics utilizing the power of mutationdetection and chromosomal microarray analysis [9]. In an inter-esting paper, Maitra narrates the applications of calcium phos-phate nanoparticles as nonviral gene-delivery vehicles, and theirpotential applications in gene therapy [10].

Final thoughtsIn the coming decade, the ability to sense and detect the stateof biologic systems and living organisms optically, electricallyand magnetically will be radically transformed by developmentsin materials physics and chemistry. Ultimately, the nanotech-nology will help us to understand the single-cell biology. Nano-technology has the potential to have a revolutionary impact oncancer diagnosis through noninvasive methods and therapy.

DisclaimerThese opinions are exclusively of the author and do not reflectthose of GeneExpression Systems, Inc. The author cited only afew references due to the space constraint.

References

1 Chan WCW, Nie SM. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281, 2016–2018 (1998).

2 Alivisatos P. The use of nanocrystals in biological detection. Nature Biotechnol. 22(1), 47–52 (2004).

3 Kim S, Lim YT, Soltesz EG et al. Near-infrared fluorescent Type II quantum dots for sentinel lymph node mapping. Nature Biotechnol. 22(1), 93–97 (2004).

4 Denisov IG, Grinkova YV, Lazarides AA, Sligar SG. Directed self-assembly of monodisperse phospholipid bilayer Nanodiscs with controlled size. J. Am. Chem. Soc. 126(11), 3477–3487 (2004).

5 Zhong Z, Wang D, Cui Y, Bockrath MW, Lieber CM. Nanowire crossbar arrays as address decoders for integrated nanosystems. Science 302, 1377–1381 (2003).

6 Silva GS, Czeisler C, Niece KL et al. Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science 2003, 1352–1355 (2004).

7 Li Y, Hong YT, Luo D. Multiplexed detection of pathogen DNA with DNA-based fluorescence nanobarcodes. Nature Biotechnol. 23(7), 885–889 (2005).

8 Jain KK. IBC’s 4th Annual Conference on Molecular Diagnostics. Expert Rev. Mol. Diagn. 5(6), 847–849 (2005).

9 Roa BB, Pulliam J, Eng CM, Cheung SW. Evolution of prenatal genetics: from point mutation testing to chromosomal microarray analysis. Expert Rev. Mol. Diagn. 5(6), 883–892 (2005).

10 Maitra A. Calcium phosphate nanoparticles: second-generation nonviral vectors in gene therapy. Expert Rev. Mol. Diagn. 5(6), 893–905 (2005).

Affiliation

• Krishnarao Appasani, PhD, MBA

GeneExpression Systems, Inc., PO Box 540170, Waltham, Massachusetts 02454–0170, USATel.: +1 781 891 8181Fax: +1 781 891 [email protected]