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Silica nanoparticles target cancer cells
RESEARCH NEWS
Silica nanoparticles target cancer cells NANOBIOTECHNOLOGY
While other nanoparticles Mesoporous silica have been used as delivery nanoparticles (MSNs) appear vehicles for drugs and proteins to show great promise with varying degrees of as a novel drug delivery success, MSNs appear to system. Two teams have have several advantages. independently reported the Firstly, the pore size can be first use of MSNs as an agent tailored to store different for administering proteins and molecules. Secondly, the pharmaceuticals directly into chemically stable inorganic human cancer cells. TEM of a mesoporous silica nanoparticle with oxide framework of the silica In one report, a team from 5.4 nm sized pores. (Courtesy of Victor S.-Y. Lin.) provides shelter so that the Ames Laboratory and Iowa molecules reach the target State University (ISU) cell unaltered, even through the acid conditions of show that MSN-encapsulated cytochrome c can be the stomach. Thirdly, MSNs are not trapped by cell internalized by human cervical cancer cells [Slowing et endosomes, which would prevent their load being al., J. Am. Chem. Soc. (2007) doi: 10.1021/ja0719780]. released into the cytoplasm of the cell, which is an Cytochrome c is a membrane-impermeable protein issue when single-walled carbon nanotubes are used as involved in apoptosis, or controlled cell death, a delivery agents. mechanism that can fail in cancer cells. A key difference between the two approaches is how In the second report, researchers at the University of the release of the protein or drug is triggered. Victor California, Los Angeles (UCLA) used MSNs to deliver S.-Y. Lin and his team at ISU put tiny caps on the end the anticancer drug camptothecin into different of the silica pores so that the release can be controlled types of human cancer cells to induce cell death – an idea that the UCLA team is also keen to explore. [Lu et al., Small (2007) doi: 10.1002/smll.200700005]. “Cancer cells overexpress antioxidant,” explains Lin. Camptothecin is insoluble in water, which is a major “That elevated antioxidant is the trigger that pops the obstacle to chemotherapy because adding solvents not cap and releases the drug.” only dilutes the potency of the drug but also creates Pauline Rigby toxicity.
Nanotube tape mimics gecko’s sticky feet CARBON MATERIALS The stickiness of adhesive tapes nanotubes to be extremely sticky based on viscoelastic glues at the nanometer level and a deteriorates over time and with good candidate to replicate gecko repeated use. Researchers from foot hairs [Yurdumakan et. al., the University of Akron and the Chem. Commun. (2005) 30, 3799]. Rensselaer Polytechnic Institute The challenge was to create a have taken inspiration from wallhierarchical nanotube structure, climbing lizards to produce an mimicking the setae and spatulas, alternative type of sticky tape that on a flexible backing. Bundles of SEM image of synthetic nanotube setae and can be used over and over again aligned nanotubes 50–500 µm wide spatulas. (Courtesy of Ali Dhinojwala.) [Ge et. al., Proc. Natl. Acad. Sci. are grown at 750°C on a catalystUSA (2007) 104, 10792]. patterned Si substrate using a mixture of ethylene and H2 gas. The nanotube bundles are then transferred onto flexible tape The feet of geckos are covered with microscopic elastic hairs to form synthetic setae. called setae, which are further split into nanometer-sized The synthetic tape supports a shear stress of 36 N/cm2, four fibers known as spatulas. Van der Waals interactions between times higher than natural gecko foot hairs, and sticks to the nanohairs on the foot and the surface on which it is hydrophobic and hydrophilic surfaces. Work is now underway placed create strong adhesive forces. The weak intermolecular to make the tape self-cleaning as well. bonds are broken and reformed as the gecko shifts its feet. Previous work at the University of Akron has shown carbon
12
AUGUST 2007 | VOLUME 2 | NUMBER 4
Paula Gould
Micelles help combat cancer NANOMEDICINE Researchers at the Chinese Academy of Sciences in Beijing have developed a self-assembled nanoscale polymer micelle containing an anticancer drug that demonstrates improved efficacy at treating human lung carcinoma over use of the drug alone [Tang, et al., J. Natl. Cancer Inst. (2007) 99, 1004]. They encapsulated doxorubicin with a block copolymer composed of poly(ethylene glycol) (PEG) and phosphatidylethanolamine (PE) to form 10–20 nm sized micelles. In vitro cultures of A549 cells, a type of human lung cancer cell, show that the doxorubicin incorporated into micelles (M-Dox) increases endocytosis into lysosomes and enhances cytotoxicity compared with the free drug. The in vivo efficacy of the micellized drug at combating tumors was monitored in mice, as was the systemic toxicity of the treatment on the animals. In both subcutaneous and pulmonary models, M-Dox increases the survival time of mice by a factor of 2–3, depending on the dose, compared with free doxorubicin or empty micelle controls. M-Dox also reduces both the size of subcutaneous tumors and the ‘tumor burden’ in diseased lungs, as well as suppressing metastasis compared with controls. Hemotherapy with doxorubicin in humans can result in severe detrimental side effects including weight loss, a reduction in white blood cell (WBC) count, and irreversible myocardiopathy. The researchers found that mice treated with M-Dox do not experience weight loss, a significant reduction in WBCs, or severe myocardiopathy. The increased survival time and antitumor effects combined with reduced negative side effects indicate this delivery method as one worthy of further investigation.
Mark E. Greene
Silica nanoparticles target cancer cells NANOBIOTECHNOLOGY
While other nanoparticles Mesoporous silica have been used as delivery nanoparticles (MSNs) appear vehicles for drugs and proteins to show great promise with varying degrees of as a novel drug delivery success, MSNs appear to system. Two teams have have several advantages. independently reported the Firstly, the pore size can be first use of MSNs as an agent tailored to store different for administering proteins and molecules. Secondly, the pharmaceuticals directly into chemically stable inorganic human cancer cells. TEM of a mesoporous silica nanoparticle with oxide framework of the silica In one report, a team from 5.4 nm sized pores. (Courtesy of Victor S.-Y. Lin.) provides shelter so that the Ames Laboratory and Iowa molecules reach the target State University (ISU) cell unaltered, even through the acid conditions of show that MSN-encapsulated cytochrome c can be the stomach. Thirdly, MSNs are not trapped by cell internalized by human cervical cancer cells [Slowing et endosomes, which would prevent their load being al., J. Am. Chem. Soc. (2007) doi: 10.1021/ja0719780]. released into the cytoplasm of the cell, which is an Cytochrome c is a membrane-impermeable protein issue when single-walled carbon nanotubes are used as involved in apoptosis, or controlled cell death, a delivery agents. mechanism that can fail in cancer cells. A key difference between the two approaches is how In the second report, researchers at the University of the release of the protein or drug is triggered. Victor California, Los Angeles (UCLA) used MSNs to deliver S.-Y. Lin and his team at ISU put tiny caps on the end the anticancer drug camptothecin into different of the silica pores so that the release can be controlled types of human cancer cells to induce cell death – an idea that the UCLA team is also keen to explore. [Lu et al., Small (2007) doi: 10.1002/smll.200700005]. “Cancer cells overexpress antioxidant,” explains Lin. Camptothecin is insoluble in water, which is a major “That elevated antioxidant is the trigger that pops the obstacle to chemotherapy because adding solvents not cap and releases the drug.” only dilutes the potency of the drug but also creates Pauline Rigby toxicity.
Nanotube tape mimics gecko’s sticky feet CARBON MATERIALS The stickiness of adhesive tapes nanotubes to be extremely sticky based on viscoelastic glues at the nanometer level and a deteriorates over time and with good candidate to replicate gecko repeated use. Researchers from foot hairs [Yurdumakan et. al., the University of Akron and the Chem. Commun. (2005) 30, 3799]. Rensselaer Polytechnic Institute The challenge was to create a have taken inspiration from wallhierarchical nanotube structure, climbing lizards to produce an mimicking the setae and spatulas, alternative type of sticky tape that on a flexible backing. Bundles of SEM image of synthetic nanotube setae and can be used over and over again aligned nanotubes 50–500 µm wide spatulas. (Courtesy of Ali Dhinojwala.) [Ge et. al., Proc. Natl. Acad. Sci. are grown at 750°C on a catalystUSA (2007) 104, 10792]. patterned Si substrate using a mixture of ethylene and H2 gas. The nanotube bundles are then transferred onto flexible tape The feet of geckos are covered with microscopic elastic hairs to form synthetic setae. called setae, which are further split into nanometer-sized The synthetic tape supports a shear stress of 36 N/cm2, four fibers known as spatulas. Van der Waals interactions between times higher than natural gecko foot hairs, and sticks to the nanohairs on the foot and the surface on which it is hydrophobic and hydrophilic surfaces. Work is now underway placed create strong adhesive forces. The weak intermolecular to make the tape self-cleaning as well. bonds are broken and reformed as the gecko shifts its feet. Previous work at the University of Akron has shown carbon
12
AUGUST 2007 | VOLUME 2 | NUMBER 4
Paula Gould
Micelles help combat cancer NANOMEDICINE Researchers at the Chinese Academy of Sciences in Beijing have developed a self-assembled nanoscale polymer micelle containing an anticancer drug that demonstrates improved efficacy at treating human lung carcinoma over use of the drug alone [Tang, et al., J. Natl. Cancer Inst. (2007) 99, 1004]. They encapsulated doxorubicin with a block copolymer composed of poly(ethylene glycol) (PEG) and phosphatidylethanolamine (PE) to form 10–20 nm sized micelles. In vitro cultures of A549 cells, a type of human lung cancer cell, show that the doxorubicin incorporated into micelles (M-Dox) increases endocytosis into lysosomes and enhances cytotoxicity compared with the free drug. The in vivo efficacy of the micellized drug at combating tumors was monitored in mice, as was the systemic toxicity of the treatment on the animals. In both subcutaneous and pulmonary models, M-Dox increases the survival time of mice by a factor of 2–3, depending on the dose, compared with free doxorubicin or empty micelle controls. M-Dox also reduces both the size of subcutaneous tumors and the ‘tumor burden’ in diseased lungs, as well as suppressing metastasis compared with controls. Hemotherapy with doxorubicin in humans can result in severe detrimental side effects including weight loss, a reduction in white blood cell (WBC) count, and irreversible myocardiopathy. The researchers found that mice treated with M-Dox do not experience weight loss, a significant reduction in WBCs, or severe myocardiopathy. The increased survival time and antitumor effects combined with reduced negative side effects indicate this delivery method as one worthy of further investigation.
Mark E. Greene