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ISSN 1743-5889 30710.2217/NNM.11.3 2011 Future Medicine Ltd Nanomedicine (2011) 6(2), 307310

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A novel device or use in identiyingearly-stage disease has been ormulated

by a team o engineers, scientists andbiologists working at Drexel University,Philadelphia, PA, USA. The carbon nan-otube-based device is able to probe singleliving cells without causing any cellulardamage and also has great potential oradvancing drug discovery.

The cellular endoscope is able to exam-ine the intracellular environment o livingcells, deliver uorescent quantum dotsand analyze molecules inside the cell, allwithout the cell recognizing the needlespresence. Drexels WM Keck Institute

or Attouidic Probes now manuacturesthe smallest endoscopes ever created,enthused Yury Gogotsi, Proessor oMaterials Science and Engineering and thedirector o the AJ Drexel NanotechnologyInstitute, PA, USA. Endoscopes providea potentially transormative technology orstudying the undamentals o single livingcells and more broadly, or cell biology.

This probe is similar to an

endoscope ... only much smaller.

Gogotsi led the research alongsideGary Friedman, Proessor o ElectricalEngineering at Drexel. We had an ideaor a minimally invasive cellular probe,the tip o which could remain withinthe cell or a long time while reportingimportant inormation in the orm ooptical and electrical signals and trans-erring tiny amounts o material to androm the cell, Friedman explained. Thisprobe is similar to an endoscope employed

by doctors to perorm minimally invasive

operations inside human patients, onlymuch smaller.

Cell biologists traditionally destroy alarge number o cells in order to extractthe components or analysis and use glasspipettes to inject material into cells, whichcause damage and are unable to reportinormation in optical or electrical or-mats. The new probe holds great promiseas a more advanced method o investigatingcellular content. Doctoral candidate andlead author o the article, Riju Singhal,reported, A cellular endoscope reportedhere is a novel, but conceptually simpledevice. It consists o a single carbon nano-

tube connected to the tips o larger glassmicropipettes that are commonly employedin biological studies, enabling them tobecome widely used in the near uture.

The team are hoping to urther developthe device and incorporate more advancedtechnology. Were now building upon themultiple demonstrated unctions o cellu-lar endoscopes to help answer elusive cellbiological questions, concluded MichaelSchrlau, Assistant Proessor o MaterialScience and Engineering at Drexel and

Director o the research laboratory o theWM Keck Institute, which partly undsthe research team through its Foundation.One application o cellular endoscopesbeing actively pursued is intracellular sur-ace-enhanced Raman spectroscopy withgold-coated endoscopes.

Sources: Drexel University, Philadelphia, PA,USA: www.drexel.edu/news/headlines/drexel-researchers-create-early-disease-detection-and-drug-delivery-device-or-single-living-cells.aspx;Singhal R, Orynbayeva Z, Kalyana Sundaram RV:Multiunctional carbon-nanotube cellular endo-

scopes. Nat. Nanotechnol. 6(1), 5764 (2011).

Novel carbon nanotube holds greatpromise or early disease detectionand drug delivery

Researchers from Drexel University have created a cellular endoscope capable

of probing single living cells without causing damage

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Gene ignition switch shows benefts incancer detection in an animal study

Researchers rom the Johns HopkinsKimmel Cancer Center, Baltimore, MD,USA, and the Virginia CommonwealthUniversity, Richmond, VA, USA, havedemonstrated the use o a gene ignitionswitch or potential use in aiding cancerdetection and treatment, in a proo-o-principle study in mice.

One approach is to use radioacve

isotopes to make cancer cellsradioacve from the inside, instead

of delivering radiaon to the

paent externally.

With current imaging devices like CTand PET, we can tell i something is wrongin a patient, but we do not have defnitivetools to distinguish cancer rom inamma-tion or inection, explained Martin Pomper,Proessor o Radiology at Johns Hopkins. Itgenerally takes at least 1 month ater giving

patients certain cancer treatments beoreexisting imaging tools can measure thepatients response to the therapy.

The switch, termed a promoter, con-sists o a set o genetic instructions encasedwithin a nanoparticle, which interacts withDNA to turn on gene activity. A promotertermed PEG-Prom was used in the experi-ments, which is only activated when insidecancer cells and not when it is present within

normal cells. PEG-Prom was connected toeither a gene that produces frey lucierase,the substance that makes freies glow, ora gene named HSV1tk, which initiates achemical reaction with radioactive labelsinside the cell that can be detected by imag-ing devices. Thus, once inside a cancer cell,the PEG-Prom switch was turned on andthe lucierase or HSV1tkgenes activated.

The PEG-Prom/gene switches wereplaced inside nanoparticles, which were inturn intravenously injected into mice with

cancer. The researchers ound that therewas a 30-old dierence in identiyingcancer cells containing lucierase (and thosecontaining the radioactive labels) and nor-mal cells that did not contain the substance.

This type o imaging technique has thepotential to add to existing tools with morespeciicity in identiying the problem,enthused Pomper. In addition to diag-nostic and monitoring tools, the technique

could be designed to deliver therapies to theheart o cancer cells. One approach is to useradioactive isotopes to make cancer cellsradioactive rom the inside, instead o deliv-ering radiation to the patient externally.

Sources: Johns Hopkins Kimmel Cancer Center,Baltimore, MD, USA: www.hopkinsmedicine.org/news/media/releases/nanoscale_gene_igni-tion_switch_may_help_spot_and_treat_cancer;Bhang HE, Gabrielson KL, Laterra Jet al.: Tumor-specifc imaging through progression elevatedgene-3 promoter-driven gene expression. Nat.Med. 17(1), 123129 (2010).

A new study has shown the success o anew biomarker in acting as a predictor odeterioration in heart ailure. The studywas carried out on patients admitted to

hospital with heart ailure at the San DiegoVeteran Aairs Medical Center, CA, USA,and a total o 144 patients with acute heartailure were ollowed rom admission to90 days postdischarge.

Heart ailure is currently the largest rea-son or admission o patients into hospitalsand traditional risk-actor prediction mod-els have only limited accuracy in identiy-ing those at highest risk. The models todate have relied upon measurements o thebiomarker pro-B-type natriuretic peptide,

but this new study shows that measuring

troponin instead has improved accuracyand allows or the detection o even smallconcentration changes.

...this new study shows thatmeasuring troponin instead [of

pro-B-type natriurec pepde]

has improved accuracy and allows

for the detecon of even small

concentraon changes.

Measurements o troponin have beenused as indicators or some types o car-diovascular disease, but by using this newhighly sensitive assay perormed on a nano-scale, levels o the biomarker could be quan-

tifed in more than 99% o serum samples

taken rom all the patients in the study.The act that 99% o our samples hadmeasurable levels highlights the easibilityo measuring troponin in virtually all heart

ailure patients, commented coinvestigatorYang Xue rom the Division o Cardiologyat the University o Caliornia at San Diego,CA, USA. This was simply not possiblewith earlier assays. But it did allow us todetect a trend o increasing troponin levelsduring the 90-day study period, which wassignifcantly associated with an increasedrisk o mortality that was not evident inpatients with stable or decreasing levels.Levels in the higher ranges were associatedwith an increased risk o mortality and

readmission, as well as higher mortality

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

A nanoparticle encasing a promoter has been demonstrated to differentiate well between cancer cells and normal cells

Highly sensitive assay demonstrates potential orpredicting heart ailure in patients

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www.futuremedicine.comfuture science group 309

About the NewsThe News highlights some o the most important events and research in the feld o nanomedicine. I you have newsworthy inormation,

please contact: Morag Robertson, Commissioning Editor, Nanomedicinem.robertson@uturemedicine.com

Combination of lethal anticancer agents within one nanobin shown to be more effective than separate delivery

rates or patients with increasing levels othe marker during treatment, comparedwith those with stable or decreasing levels.

As Xue concluded, Heart ailure is acomplex disease and no single biomarkeris likely to be ully predictive. However,

because troponin is a marker or myocar-dial damage (a signifcant cause o heartailure), its accurate measurement in

Image courtesy of Sang-Min Lee and SonBinh Nguyen, NorthwesternUniversity, IL, USA.

A team o investigators rom NorthwesternUniversity, Evanston, IL, USA, have dem-onstrated that a synergistic eect can beachieved when using nanoparticles to delivermultiple drugs simultaneously, thus enhanc-ing the cell-killing ability o both drugs. Thestudy was led by SonBinh T Nguyen andThomas V OHalloran rom NorthwesternUniversity (NU). Nguyen and OHalloranwere coprincipal investigators on a recentCenter Cancer Nanotechnology Excellence(CCNE) grant to the Robert H Lurie

Comprehensive Cancer Center (RHLCCC)and the Northwestern Nanoscale Scienceand Engineering Center (NSEC). Theyare also coprincipal investigators on oneo 12 Cancer Nanotechnology PlatormPartnerships unded by the National CancerInstitute Alliance or Nanotechnologyin Cancer.

This is a highly aracve concept in

personalized medicine, especially as

it relates to cancer treatment, where

the stakes are becoming increasinglybigger, to know that the therapy is

working in real me.

The novel therapeutic developed by theNU team consists o a polymer nanoparticlecontaining a combination o cisplatin anddoxorubicin, two powerul and highlytoxic anticancer agents. Not only did the

combination demonstrate an enhancedability in destroying tumors, but the two-in-one nanoparticle also has great potentialor reduced side eects associated with thedrugs, since the amount needed to achievethe desired efcacy is much less or eachdrug. Such simultaneous delivery o twodrugs to tumor cells can also reduce thechance or single-drug resistance to develop,Nguyen explained.

Cross-section of the polymer-caged nanobins drug-delivery platform showing adrug-encapsulated liposome core and a crosslinked polymer cage (not drawn toscale) that serves as a reservoir for additional drugs, imaging agents andtargeting ligands.

combination with other biomarkers willhelp provide a more comprehensive evalu-ation and certainly more accurate thanB-type natriuretic peptide alone.

Sources: University o Caliornia, San Diego, CA,USA: http://med.ucsd.edu/aculty.shtml; Xue Y,

Clopton P, Peacock WF et al.: Serial changesin high-sensitive troponin I predict outcome inpatients with decompensated heart ailure. Eur.J. Heart Fail. 13(1), 3742 (2011).

Nanotherapeutic shows great potential or increasedkilling o cancer cells

The nanoparticles, named polymer-caged nanobins (PCNs) by the NUresearchers, consist o a liposome encasedwithin a pH-responsive polymer cage.Doxorubicin was entrapped within theliposomes core, whilst cisplatin wasentrapped within the polymer cage. As thenext generation o the nanobins that wasoriginally designed to carry arsenic trioxideto solid tumors, PCNs have proved to be

Drug

O NH

O Pt

N

NHO

H3

N

NH3

O

O

O NH

O OH

Bio-compatible polymers

O

O

O NH

NH

O

Cross-linking,

stability

Secondary drug

Imaging agents

Solubility,pH-sensitive

groups

Targetingligands

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two drugs appeared to work synergisti-cally, urther proving the exciting possibil-ity or administering the two drugs withinthe same nanoparticle.

Recently, the NU team has collaboratedwith Thomas Meade, another NU-CCNE

principal investigator, to tag PCNs withgadolinium-based MRI agents to createnovel theranostic constructs that shouldenable both drugs and imaging agent tobe delivered to the disease tissue at thesame time, allowing the disease site tobe monitored as the drug is released inreal time. In this way, clinical treatmentdecisions can be adjusted mid-therapy,in direct response to the cancer response.This is a highly attractive concept in per-sonalized medicine, especially as it relates

to cancer treatment, where the stakes are

becoming increasingly bigger, to knowthat the therapy is working in real time.As Nguyen concluded, Beyond enhancedchemotherapeutics, the PCN platormholds great promise or the developmento other combination therapies.

Sources: Lee SM, Song Y, Hong BJet al.: Modularpolymer-caged nanobins as a theranostic plat-orm with enhanced magnetic resonance relax-ivity and pH-responsive drug-release. Angew.Chem. Int. Ed. 49, 99609964 (2010); NationalCancer Institute, Alliance or Nanotechnologyin Cancer, Bethesda, MD, USA: http://nano.cancer.gov/action/news/2010/dec/nanotech_news_20101216e.asp; Lee SM, OHalloran TV,Nguyen ST: Polymer-caged nanobins or syner-gistic cisplatin-doxorubicin combination chemo-therapy. J. Am. Chem. Soc. 132, 1713017138(2010) .

quite versatile in their ability to deliver alarge range o drugs to cancer targets, rang-ing rom doxorubicin and gemcitabine tocisplatin and arsenic trioxide.

The NU researchers initially ound thata ratio o 5:1 o cisplatin to doxorubicinwas most eective in treating ovariantumors when the two drugs were com-bined in the same nanoparticle. By com-parison, administering the two drugs intwo separate nanoparticles resulted in lesseective destruction o malignant cells,

even at the same ratio. Remarkably, the