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Nanoparticles seek out and destroy cancer
RESEARCH NEWS
Nanoparticles seek out and destroy cancer NANOTECHNOLOGY/BIOMATERIALS
A quantum dot probe for targeting and imaging cancer. (Courtesy of Xiaohu Gao.)
The unique chemical and physical properties of nanoparticles can be tailored to give smart biomaterials with great potential for targeting, imaging, and treating cancer in vivo, as two recent reports demonstrate. Xiaohu Gao and researchers at Emory University, Georgia Institute of Technology, and Cambridge Research & Instrumentation, Inc. used semiconductor quantum dots (QDs) to target and image tumors in mice [Gao et al., Nat. Biotech. (2004) 22, 969]. The QDs are encapsulated by a protective coat consisting of a coordinating ligand and an amphiphilic polymer. “This is very important to prevent particle degradation under complex in vivo conditions,” explains Gao. Tumor-targeting antibodies and poly(ethylene glycol) (PEG) molecules are then attached to give a multifunctional nanoparticle probe. QD probes carrying an antibody for a human prostate cancer marker were injected into mice bearing these tumors. Wavelength-resolved spectral imaging allows the orange-red QD fluorescence to be detected over the green autofluorescence of mouse skin. The
imaging reveals that QDs are successfully delivered to the tumors by, the researchers suggest, two different targeting mechanisms. The antibody-conjugated QDs ‘actively’ recognize the tumor cells, but the nanoparticles passively accumulate in tumors as well because the blood vessels are more ‘leaky’ than in ordinary tissues. “This is the first time that bioconjugated QDs have been used for simultaneous targeting and imaging of tumors in living animals,” says Gao. Jennifer L. West and colleagues at Rice University and Nanospectra Biosciences, Inc. have also demonstrated the use of nanoparticles in cancer treatment [O’Neal et al., Cancer Lett. (2004) 209, 171]. The therapy makes use of injected ‘nanoshells’ that, like Gao’s QD probes, enter tumors through their permeable blood vessels and accumulate. The nanoshells consist of a silica core and an ultrathin Au shell with relative thicknesses can be tuned to give an absorption peak in the near infrared. Laser light of this frequency penetrates deep into tissues, where the Au shell efficiently converts absorbed light to heat, destroying the surrounding tumor cells. The researchers used this nanoshell-assisted photothermal therapy (NAPT) on mice in which tumors had been grown. All treated tumors abated, and the mice remained free of tumors for over 90 days. “We are extremely encouraged by the results of these first animal tests,” said West. This targeted, minimally invasive therapy is simple to perform and could be used in vital regions where surgery is not feasible. “While we don’t yet have a target date for our first human trial, our entire team is working hard to make this treatment available to cancer patients as soon as possible,” says Naomi J. Halas. Jonathan Wood
Mother-of-pearl reveals her tough side BIOMATERIALS Xiaodong Li and colleagues at the University of South Carolina, Chung Yuan Christian University, Taiwan, and the University of British Columbia, Canada have characterized the structure and mechanical properties of seashells in order to understand their extraordinary toughness [Li et al., Nano Lett. (2004) 4 (4), 613]. Nature has evolved complex bottom-up methods for fabricating ordered nanostructured materials ideally suited to their functions. For example, motherof-pearl or nacre is a remarkably robust
12
September 2004
nanocomposite despite the brittle nature of its components. It is made up of ~95% aragonite, a mineral form of CaCO3, and a few percent organic biopolymers, but the composite has a toughness 1000 times greater than its constituents. Nacre is known to have a ‘bricks and mortar’ structure with aragonite platelets held together by biopolymer glue. The platelets were thought to be single crystals, based on their electron diffraction pattern. Li and colleagues used atomic force and scanning electron microscopy to show,
for the first time, that individual platelets consist of ‘cobble-like’, polygonal nanosized grains. During biomineralization, nanoparticles aggregate into platelets with the same crystal orientation. The researchers also show the platelets are ductile, not brittle – a property that could result from the large number of nanograins. Indentations made with a microindenter produce short, radial cracks that propagate along the biopolymer mortar layers. Around the crack tip, the
platelets are plastically deformed. “This will change our conventional concept of nacre aragonite platelets,” says Li. “The discovery of deformability of platelets is of critical importance to understanding the secret of ultrahigh fracture toughness for seashells.” Understanding how nacre’s structure and toughness are related could enable the development of synthetic nanocomposites that reproduce some of these properties. Jonathan Wood
Nanoparticles seek out and destroy cancer NANOTECHNOLOGY/BIOMATERIALS
A quantum dot probe for targeting and imaging cancer. (Courtesy of Xiaohu Gao.)
The unique chemical and physical properties of nanoparticles can be tailored to give smart biomaterials with great potential for targeting, imaging, and treating cancer in vivo, as two recent reports demonstrate. Xiaohu Gao and researchers at Emory University, Georgia Institute of Technology, and Cambridge Research & Instrumentation, Inc. used semiconductor quantum dots (QDs) to target and image tumors in mice [Gao et al., Nat. Biotech. (2004) 22, 969]. The QDs are encapsulated by a protective coat consisting of a coordinating ligand and an amphiphilic polymer. “This is very important to prevent particle degradation under complex in vivo conditions,” explains Gao. Tumor-targeting antibodies and poly(ethylene glycol) (PEG) molecules are then attached to give a multifunctional nanoparticle probe. QD probes carrying an antibody for a human prostate cancer marker were injected into mice bearing these tumors. Wavelength-resolved spectral imaging allows the orange-red QD fluorescence to be detected over the green autofluorescence of mouse skin. The
imaging reveals that QDs are successfully delivered to the tumors by, the researchers suggest, two different targeting mechanisms. The antibody-conjugated QDs ‘actively’ recognize the tumor cells, but the nanoparticles passively accumulate in tumors as well because the blood vessels are more ‘leaky’ than in ordinary tissues. “This is the first time that bioconjugated QDs have been used for simultaneous targeting and imaging of tumors in living animals,” says Gao. Jennifer L. West and colleagues at Rice University and Nanospectra Biosciences, Inc. have also demonstrated the use of nanoparticles in cancer treatment [O’Neal et al., Cancer Lett. (2004) 209, 171]. The therapy makes use of injected ‘nanoshells’ that, like Gao’s QD probes, enter tumors through their permeable blood vessels and accumulate. The nanoshells consist of a silica core and an ultrathin Au shell with relative thicknesses can be tuned to give an absorption peak in the near infrared. Laser light of this frequency penetrates deep into tissues, where the Au shell efficiently converts absorbed light to heat, destroying the surrounding tumor cells. The researchers used this nanoshell-assisted photothermal therapy (NAPT) on mice in which tumors had been grown. All treated tumors abated, and the mice remained free of tumors for over 90 days. “We are extremely encouraged by the results of these first animal tests,” said West. This targeted, minimally invasive therapy is simple to perform and could be used in vital regions where surgery is not feasible. “While we don’t yet have a target date for our first human trial, our entire team is working hard to make this treatment available to cancer patients as soon as possible,” says Naomi J. Halas. Jonathan Wood
Mother-of-pearl reveals her tough side BIOMATERIALS Xiaodong Li and colleagues at the University of South Carolina, Chung Yuan Christian University, Taiwan, and the University of British Columbia, Canada have characterized the structure and mechanical properties of seashells in order to understand their extraordinary toughness [Li et al., Nano Lett. (2004) 4 (4), 613]. Nature has evolved complex bottom-up methods for fabricating ordered nanostructured materials ideally suited to their functions. For example, motherof-pearl or nacre is a remarkably robust
12
September 2004
nanocomposite despite the brittle nature of its components. It is made up of ~95% aragonite, a mineral form of CaCO3, and a few percent organic biopolymers, but the composite has a toughness 1000 times greater than its constituents. Nacre is known to have a ‘bricks and mortar’ structure with aragonite platelets held together by biopolymer glue. The platelets were thought to be single crystals, based on their electron diffraction pattern. Li and colleagues used atomic force and scanning electron microscopy to show,
for the first time, that individual platelets consist of ‘cobble-like’, polygonal nanosized grains. During biomineralization, nanoparticles aggregate into platelets with the same crystal orientation. The researchers also show the platelets are ductile, not brittle – a property that could result from the large number of nanograins. Indentations made with a microindenter produce short, radial cracks that propagate along the biopolymer mortar layers. Around the crack tip, the
platelets are plastically deformed. “This will change our conventional concept of nacre aragonite platelets,” says Li. “The discovery of deformability of platelets is of critical importance to understanding the secret of ultrahigh fracture toughness for seashells.” Understanding how nacre’s structure and toughness are related could enable the development of synthetic nanocomposites that reproduce some of these properties. Jonathan Wood