RESEARCH NEWS

AUGUST 2007 | VOLUME 2 | NUMBER 412

Silica nanoparticles target cancer cells

Mesoporous silica

nanoparticles (MSNs) appear

to show great promise

as a novel drug delivery

system. Two teams have

independently reported the

first use of MSNs as an agent

for administering proteins and

pharmaceuticals directly into

human cancer cells.

In one report, a team from

Ames Laboratory and Iowa

State University (ISU)

show that MSN-encapsulated cytochrome c can be

internalized by human cervical cancer cells [Slowing et al., J. Am. Chem. Soc. (2007) doi: 10.1021/ja0719780].

Cytochrome c is a membrane-impermeable protein

involved in apoptosis, or controlled cell death, a

mechanism that can fail in cancer cells.

In the second report, researchers at the University of

California, Los Angeles (UCLA) used MSNs to deliver

the anticancer drug camptothecin into different

types of human cancer cells to induce cell death

[Lu et al., Small (2007) doi: 10.1002/smll.200700005].

Camptothecin is insoluble in water, which is a major

obstacle to chemotherapy because adding solvents not

only dilutes the potency of the drug but also creates

toxicity.

While other nanoparticles

have been used as delivery

vehicles for drugs and proteins

with varying degrees of

success, MSNs appear to

have several advantages.

Firstly, the pore size can be

tailored to store different

molecules. Secondly, the

chemically stable inorganic

oxide framework of the silica

provides shelter so that the

molecules reach the target

cell unaltered, even through the acid conditions of

the stomach. Thirdly, MSNs are not trapped by cell

endosomes, which would prevent their load being

released into the cytoplasm of the cell, which is an

issue when single-walled carbon nanotubes are used as

delivery agents.

A key difference between the two approaches is how

the release of the protein or drug is triggered. Victor

S.-Y. Lin and his team at ISU put tiny caps on the end

of the silica pores so that the release can be controlled

– an idea that the UCLA team is also keen to explore.

“Cancer cells overexpress antioxidant,” explains Lin.

“That elevated antioxidant is the trigger that pops the

cap and releases the drug.”

Pauline Rigby

NANOBIOTECHNOLOGY

TEM of a mesoporous silica nanoparticle with

5.4 nm sized pores. (Courtesy of Victor S.-Y. Lin.)

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

Micelles help combat cancerNANOMEDICINE

Nanotube tape mimics gecko’s sticky feet

The stickiness of adhesive tapes

based on viscoelastic glues

deteriorates over time and with

repeated use. Researchers from

the University of Akron and the

Rensselaer Polytechnic Institute

have taken inspiration from wall-

climbing lizards to produce an

alternative type of sticky tape that

can be used over and over again

[Ge et. al., Proc. Natl. Acad. Sci.

USA (2007) 104, 10792].

The feet of geckos are covered with microscopic elastic hairs

called setae, which are further split into nanometer-sized

fibers known as spatulas. Van der Waals interactions between

the nanohairs on the foot and the surface on which it is

placed create strong adhesive forces. The weak intermolecular

bonds are broken and reformed as the gecko shifts its feet.

Previous work at the University of Akron has shown carbon

nanotubes to be extremely sticky

at the nanometer level and a

good candidate to replicate gecko

foot hairs [Yurdumakan et. al.,

Chem. Commun. (2005) 30, 3799].

The challenge was to create a

hierarchical nanotube structure,

mimicking the setae and spatulas,

on a flexible backing. Bundles of

aligned nanotubes 50–500 µm wide

are grown at 750°C on a catalyst-

patterned Si substrate using a mixture of ethylene and H2 gas.

The nanotube bundles are then transferred onto flexible tape

to form synthetic setae.

The synthetic tape supports a shear stress of 36 N/cm2, four

times higher than natural gecko foot hairs, and sticks to

hydrophobic and hydrophilic surfaces. Work is now underway

to make the tape self-cleaning as well.

Paula Gould

CARBON MATERIALS

SEM image of synthetic nanotube setae and

spatulas. (Courtesy of Ali Dhinojwala.)

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