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Posted: Dec 10, 2010

Another nanotechnology step towards 'Fantastic Voyage'

(Nanowerk Spotlight) Several nanoparticle drugs are now in clinical trials, and many more are being developed in research labs. These particles hold great potential to improve the performance of existing cancer drugs. By functionalizing the nanoparticle surface with tumor-specific targeting ligands (specific proteins found in large quantities on tumor cells), scientists can actively target nanoparticles and their payload to desired tumor targets (see for instance: "Cancer scientists believe nanoparticles could accurately target tumors, avoiding side effects").
However, off-targeting remains a key challenge of nanotechnology researchers working on nanoparticle drug delivery – the majority of intravenously administered therapeutic nanoparticles are also reaching normal tissues, resulting in considerable adverse side effects. Another challenge of nanoparticle drug delivery includes the limited penetration depth of particles into the tumors.
While extensive efforts have been devoted for designing therapeutic nanoparticles, a new study by researchers in the U.S. – echoing the journey through the human body in Fantastic Voyage – represents the first example of coupling such drug nanocarriers with self-propelled nanoshuttles.
"The ability of synthetic nanomotors to carry 'cargo' was demonstrated recently by Sen and Wang groups but not in connection to common drug-loaded particles," Joseph Wang tells Nanowerk. "In our new study, we demonstrated that catalytic nanoshuttles can readily pickup common biocompatible and biodegradable drug-loaded Poly D,L-lactic-co-glycolic acid (PLGA) particles and liposomes and transport them over predefined routes towards predetermined destination."
Wang, who runs the Laboratory for Nanobioelectronics at the Department of NanoEngineering at UC San Diego, and his group have worked with Liangfang Zhang' team from the Department of Nanoengineering and Moores Cancer Center at UC San Diego to demonstrate an initial proof-of-concept of nanoshuttle drug-delivery transport. While Wang's team has expertise in nanomotors (see "Are nanotechnology machines a match for nature's biomotors?"), Zhang's group specializes in directed drug delivery.
"We are all motivated towards the realizing the vision of the 1966 movie 'Fantastic Voyage' vision and by the potential to enhance medical treatment" Wang tells Nanowerk.
Their proof-of-concept, involving the directed delivery of common polymeric and liposomal drug carriers using catalytic nanomotors, has recently been published in Small ("Rapid Delivery of Drug Carriers Propelled and Navigated by Catalytic Nanoshuttles").
Translocation of model drug carriers by catalytic nanowire motors
Translocation of model drug carriers by catalytic nanowire motors. (Image: Joseph Wang, UCSD)
"We showed our nanomotors to pick, transport and release varying sized drug carriers from a loading zone to a predetermined destination through a predefined route" explains Wang. "The transport rate of the drug carriers delivered by a nanomotor is more than three orders of magnitude faster than that expected from Brownian motion."
He points out, though, that while the concept of nanoshuttle drug-delivery transport is illustrated here using catalytic nanomotors, practical in vivo applications would require the use of fuel-free motors.
To build their devices, the team synthesized drug-loaded PLGA particles containing small magnetic iron oxide nanoparticles and applied them as cargo to catalytic nanowire motors (read more on these motors: "Catalytic nanotransporters for nanotechnology applications outside biological systems").
The image above illustrates the scheme of the pick-up, transport and release of drug-loaded PLGA microparticles by synthetic nanomotors.
Zhang notes that the overall rapid transport of polymeric particles delivered by nanoshuttles can be advantageous for the drug carriers to reach deep tumor tissues, compared with common nanoparticle drug delivery whose penetration depth mainly depends on Brownian motion once the particles are in the tumor interstitium.
The straight-line images in this movie visually depict the effect of the PLGA particle size on the transport rate using catalytic nanomotors.
"The strong propelling force provided by the nanoshuttles can potentially facilitate the tissue penetration of drug carriers," he says. "Moreover, these nanomotor-guided nanoparticle drug delivery can also minimize the undesirable off-target effects of the current nanoparticle drug delivery systems."
The use of catalytic nanoshuttles to navigate and propel drug carriers represents a significant step towards the applications of man-made nanomotors for the treatment of systemic diseases. The success of this work will eventually facilitate the delivery of therapeutic and diagnostic agents to areas of the body that are currently inaccessible.
Wang and Zhang say that the future directions of their research aim at improving the current nanoshuttles and translating this concept for more clinically relevant applications. Realizing these goals will require proper attention to major issues such as developing fuel free nanomotors that can be solely driven by magnetic fields, effectively releasing the therapeutic nanoparticle cargos at the sites of actions, and removing nanomotors from the body after completing the mission.
While key challenges remain prior to applying these nanomotors for in vivo targeted drug delivery, this work advances one step closer to the futuristic nanomachine for systemic medical applications.
Reference: Kagan, D., Laocharoensuk, R., Zimmerman, M., Clawson, C., Balasubramanian, S., Kang, D., Bishop, D., Sattayasamitsathit, S., Zhang, L., & Wang, J. (2010). Rapid Delivery of Drug Carriers Propelled and Navigated by Catalytic Nanoshuttles Small, 6 (23), 2741-2747 DOI: 10.1002/smll.201001257
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