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Nanomedicine
News
Novel carbon nanotube holds great
promise for early disease detection
and drug delivery
Research Highlights Researchers from Drexel University have created a ‘cellular endoscope’ capable
of probing single living cells without causing damage

A novel device for use in identifying operations inside human patients, only
early-stage disease has been formulated much smaller.”
by a team of engineers, scientists and Cell biologists traditionally destroy a
biologists working at Drexel University, large number of cells in order to extract
Philadelphia, PA, USA. The carbon nan- the components for ana­lysis and use glass
otube-based device is able to probe single pipettes to inject material into cells, which
living cells without causing any cellular cause damage and are unable to report
damage and also has great potential for information in optical or electrical for-
advancing drug discovery. mats. The new probe holds great promise
The ‘cellular endoscope’ is able to exam- as a more advanced method of investigating
ine the intracellular environment of living cellular content. Doctoral candidate and
cells, deliver fluorescent quantum dots lead author of the article, Riju Singhal,
and analyze molecules inside the cell, all reported, “A cellular endoscope reported
without the cell recognizing the needle’s here is a novel, but conceptually simple
presence. “Drexel’s WM Keck Institute device. It consists of a single carbon nano-
for Attofluidic Probes now manufactures tube connected to the tips of larger glass
the smallest endoscopes ever created,” micropipettes that are commonly employed
enthused Yury Gogotsi, Professor of in biological studies, enabling them to
Materials Science and Engineering and the become widely used in the near future.”
director of the AJ Drexel Nanotechnology The team are hoping to further develop
Institute, PA, USA. “Endoscopes provide the device and incorporate more advanced
a potentially transformative technology for technology. “We’re now building upon the
studying the fundamentals of single living multiple demonstrated functions of cellu-
cells and more broadly, for cell biology.” lar endoscopes to help answer elusive cell
biological questions,” concluded Michael
“This probe is similar to an Schrlau, Assistant Professor of Material
e­ndoscope ... only much smaller.” Science and Engineering at Drexel and
Director of the research laboratory of the
Gogotsi led the research alongside WM Keck Institute, which partly funds
Gary Friedman, Professor of Electrical the research team through its Foundation.
Engineering at Drexel. “We had an idea “One application of cellular endoscopes
for a minimally invasive cellular probe, being actively pursued is intracellular sur-
the tip of which could remain within face-enhanced Raman spectroscopy with
the cell for a long time while reporting gold-coated endoscopes.”
important information in the form of Sources: Drexel University, Philadelphia, PA,
optical and electrical signals and trans- USA: www.drexel.edu/news/headlines/drexel-
ferring tiny amounts of material to and researchers-create-early-disease-detection-and-
from the cell,” Friedman explained. “This drug-delivery-device-for-single-living-cells.aspx;
part of
Singhal R, Orynbayeva Z, Kalyana Sundaram RV:
probe is similar to an endoscope employed Multifunctional carbon-nanotube cellular endo-
by doctors to perform minimally invasive scopes. Nat. Nanotechnol. 6(1), 57–64 (2011).

10.2217/NNM.11.3 © 2011 Future Medicine Ltd Nanomedicine (2011) 6(2), 307–310 ISSN 1743-5889 307
News & Views – News

Gene ‘ignition switch’ shows benefits in


cancer detection in an animal study
A nanoparticle encasing a promoter has been demonstrated to differentiate well between cancer cells and normal cells

Researchers from the Johns Hopkins patients certain cancer treatments before cancer. The researchers found that there
Kimmel Cancer Center, Baltimore, MD, existing imaging tools can measure the was a 30-fold difference in identifying
USA, and the Virginia Commonwealth patient’s response to the therapy.” cancer cells containing luciferase (and those
University, Richmond, VA, USA, have The switch, termed a promoter, con- containing the radioactive labels) and nor-
demonstrated the use of a gene ‘ignition sists of a set of genetic instructions encased mal cells that did not contain the substance.
switch’ for potential use in aiding cancer within a nanoparticle, which interacts with “This type of imaging technique has the
detection and treatment, in a proof-of- DNA to turn on gene activity. A promoter potential to add to existing tools with more
principle study in mice. termed PEG-Prom was used in the experi- specificity in identifying the problem,”
ments, which is only activated when inside enthused Pomper. “In addition to diag-
“One approach is to use r­adioactive cancer cells and not when it is present within nostic and monitoring tools, the technique
isotopes to make cancer cells normal cells. PEG-Prom was connected to could be designed to deliver therapies to the
radioactive from the inside, instead either a gene that produces firefly luciferase, heart of cancer cells. One approach is to use
of delivering radiation to the the substance that makes fireflies glow, or radioactive isotopes to make cancer cells
patient externally.” a gene named HSV1tk, which initiates a radioactive from the inside, instead of deliv-
chemical reaction with radioactive labels ering radiation to the patient externally.”
“With current imaging devices like CT inside the cell that can be detected by imag- Sources: Johns Hopkins Kimmel Cancer Center,
and PET, we can tell if something is wrong ing devices. Thus, once inside a cancer cell, Baltimore, MD, USA: www.hopkinsmedicine.
in a patient, but we do not have definitive the PEG-Prom switch was turned on and org/news/media/releases/nanoscale_gene_igni-
tools to distinguish cancer from inflamma- the luciferase or HSV1tk genes activated. tion_switch_may_help_spot_and_treat_cancer;
Bhang HE, Gabrielson KL, Laterra J et al.: Tumor-
tion or infection,” explained Martin Pomper, The PEG-Prom/gene switches were specific imaging through progression elevated
Professor of Radiology at Johns Hopkins. “It placed inside nanoparticles, which were in gene-3 promoter-driven gene expression. Nat.
generally takes at least 1 month after giving turn intravenously injected into mice with Med. 17(1), 123–129 (2010).

Highly sensitive assay demonstrates potential for


p­redicting heart failure in patients
Measuring troponin levels proves to be an accurate way of monitoring risks associated with heart failure

A new study has shown the success of a troponin instead has improved accuracy taken from all the patients in the study.
new biomarker in acting as a predictor of and allows for the detection of even small “The fact that 99% of our samples had
deterioration in heart failure. The study concentration changes. measurable levels highlights the feasibility
was carried out on patients admitted to of measuring troponin in virtually all heart
hospital with heart failure at the San Diego “...this new study shows that failure patients,” commented coinvestigator
Veteran Affairs Medical Center, CA, USA, m­easuring troponin instead [of Yang Xue from the Division of Cardiology
and a total of 144 patients with acute heart pro-B-type natriuretic peptide] at the University of California at San Diego,
failure were followed from admission to has improved accuracy and allows CA, USA. “This was simply not possible
90 days postdischarge. for the detection of even small with earlier assays. But it did allow us to
Heart failure is currently the largest rea- concentration changes.” detect a trend of increasing troponin levels
son for admission of patients into hospitals during the 90‑day study period, which was
and traditional risk-factor prediction mod- Measurements of troponin have been significantly associated with an increased
els have only limited accuracy in identify- used as indicators for some types of car- risk of mortality that was not evident in
ing those at highest risk. The models to diovascular disease, but by using this new patients with stable or decreasing levels.”
date have relied upon measurements of the highly sensitive assay performed on a nano- Levels in the higher ranges were associated
biomarker pro-B-type natriuretic peptide, scale, levels of the biomarker could be quan- with an increased risk of mortality and
but this new study shows that measuring tified in more than 99% of serum samples readmission, as well as higher mortality

308 Nanomedicine (2011) 6(2) future science group


News – News & Views
rates for patients with increasing levels of combination with other biomarkers will
the marker during treatment, compared help provide a more comprehensive evalu-
with those with stable or decreasing levels. ation – and certainly more accurate than
As Xue concluded, “Heart failure is a B-type natriuretic peptide alone.”
complex disease and no single biomarker Sources: University of California, San Diego, CA,
is likely to be fully predictive. However, USA: http://med.ucsd.edu/faculty.shtml; Xue Y,
because troponin is a marker for myocar- Clopton P, Peacock WF et  al.: Serial changes
dial damage (a significant cause of heart in high-sensitive troponin I predict outcome in
patients with decompensated heart failure. Eur.
failure), its accurate measurement in J. Heart Fail. 13(1), 37–42 (2011).

Nanotherapeutic shows great potential for increased


killing of cancer cells
Combination of lethal anticancer agents within one ‘nanobin’ shown to be more effective than separate delivery

A team of investigators from Northwestern combination demonstrate an enhanced The nanoparticles, named polymer-­
University, Evanston, IL, USA, have dem- ability in destroying tumors, but the two- caged nanobins (PCNs) by the NU
onstrated that a synergistic effect can be in-one nanoparticle also has great potential researchers, consist of a liposome encased
achieved when using nanoparticles to deliver for reduced side effects associated with the within a pH-responsive polymer cage.
multiple drugs simultaneously, thus enhanc- drugs, since the amount needed to achieve Doxorubicin was entrapped within the
ing the cell-killing ability of both drugs. The the desired efficacy is much less for each liposome’s core, whilst cisplatin was
study was led by SonBinh T Nguyen and drug. “Such simultaneous delivery of two entrapped within the polymer cage. As the
Thomas V O’Halloran from Northwestern drugs to tumor cells can also reduce the next generation of the nanobins that was
University (NU). Nguyen and O’Halloran chance for single-drug resistance to develop,” originally designed to carry arsenic tri­oxide
were coprincipal investigators on a recent Nguyen explained. to solid tumors, PCNs have proved to be
Center Cancer Nanotechnology Excellence
Bio-compatible polymers
(CCNE) grant to the Robert  H Lurie
Comprehensive Cancer Center (RHLCCC)
and the Northwestern Nano­scale Science O OH
H
O NH H O N
and Engineering Center (NSEC). They O N Solubility,
are also coprincipal investigators on one O NH pH-sensitive
groups
of 12  Cancer Nanotechnology Platform
Partnerships funded by the National Cancer O Imaging agents
Drug Targeting
Institute Alliance for Nanotechnology
O ligands
in Cancer. O
O
N
“This is a highly attractive concept in O Pt NH
personalized medicine, especially as NH Cross-linking, 3
H3N
it relates to cancer treatment, where stability
the stakes are becoming increasingly O Secondary drug
bigger, to know that the therapy is
working in real time.”
Cross-section of the polymer-caged nanobins drug-delivery platform showing a
The novel therapeutic developed by the drug-encapsulated liposome core and a crosslinked polymer cage (not drawn to
NU team consists of a polymer nano­particle scale) that serves as a reservoir for additional drugs, imaging agents and
containing a combination of cisplatin and targeting ligands.
doxorubicin, two powerful and highly Image courtesy of Sang-Min Lee and SonBinh Nguyen, Northwestern
toxic anticancer agents. Not only did the University, IL, USA.

„„ About the News


The News highlights some of the most important events and research in the field of nanomedicine. If you have newsworthy ­information,
please contact: Morag Robertson, Commissioning Editor, Nanomedicine m.robertson@futuremedicine.com

future science group www.futuremedicine.com 309


News & Views – News
two drugs appeared to work synergisti- becoming increasingly bigger, to know
cally, further proving the exciting possibil- that the therapy is working in real time.
ity for administering the two drugs within As Nguyen concluded, “Beyond enhanced
the same nanoparticle. chemotherapeutics, the PCN platform
Recently, the NU team has collaborated holds great promise for the development
with Thomas Meade, another NU-CCNE of other combination therapies.”
quite versatile in their ability to deliver a principal investigator, to tag PCNs with
large range of drugs to cancer targets, rang- gadolinium-based MRI agents to create
Sources: Lee SM, Song Y, Hong BJ et al.: Modular
ing from doxorubicin and gemcitabine to novel theranostic constructs that should polymer-caged nanobins as a theranostic plat-
cisplatin and arsenic trioxide. enable both drugs and imaging agent to form with enhanced magnetic resonance relax-
The NU researchers initially found that be delivered to the disease tissue at the ivity and pH-responsive drug-release. Angew.
Chem. Int. Ed. 49, 9960–9964 (2010); National
a ratio of 5:1 of cisplatin to doxorubicin same time, allowing the disease site to
Cancer Institute, Alliance for Nanotechnology
was most effective in treating ovarian be monitored as the drug is released in in Cancer, Bethesda, MD, USA: http://nano.
tumors when the two drugs were com- real time. In this way, clinical treatment cancer.gov/action/news/2010/dec/nanotech_
bined in the same nanoparticle. By com- decisions can be adjusted mid-therapy, news_2010–12–16e.asp; Lee SM, O’Halloran TV,
Nguyen ST: Polymer-caged nanobins for syner-
parison, administering the two drugs in in direct response to the cancer response.
gistic cisplatin-doxorubicin combination chemo-
two separate nanoparticles resulted in less This is a highly attractive concept in per- therapy. J. Am. Chem. Soc. 132, 17130–17138
effective destruction of malignant cells, sonalized medicine, especially as it relates (2010) .
even at the same ratio. Remarkably, the to cancer treatment, where the stakes are

310 Nanomedicine (2011) 6(2) future science group