Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeting strategy may open door to better cancer drug delivery

07.06.2018

Bioengineers may be able to use the unique mechanical properties of diseased cells, such as metastatic cancer cells, to help improve delivery of drug treatments to the targeted cells, according to a team of researchers at Penn State.

Many labs around the world are developing nanoparticle-based, drug delivery systems to selectively target tumors. They rely on a key-and-lock system in which protein keys on the surface of the nanoparticle click into the locks of a highly expressed protein on the surface of the cancer cell. The cell membrane then wraps around the nanoparticle and ingests it. If enough of the nanoparticles and their drug cargo is ingested, the cancer cell will die.


In the transition from benign to malignant, cancer cells transition from stiff to soft. Mechanotargeting harnesses mechanics to improve targeting efficiency of nanparticle-based therapeutic agents.

Credit: Zhang lab/vecteezy.com

The adhesive force of the lock and key is what drives the nanoparticle into the cell, said Sulin Zhang, professor of engineering science and mechanics.

"It is almost universal that whenever there is a driving force for a process, there always is a resistive force," Zhang said. "Here, the driving force is biochemical -- the protein-protein interaction."

The resistive force is the mechanical energy cost required for the membrane to wrap around the nanoparticle. Until now, bioengineers only considered the driving force and designed nanoparticles to optimize the chemical interactions, a targeting strategy called "chemotargeting." Zhang believes they should also take into account the mechanics of the cells to design nanoparticles to achieve enhanced targeting, which forms a new targeting strategy called "mechanotargeting."

"These two targeting strategies are complementary; you can combine chemotargeting and mechanotargeting to achieve the full potential of nanoparticle-based diagnostic and therapeutic agents," Zhang said. "The fact is that targeting efficiency requires a delicate balance between driving and resistive forces. For instance, if there are too many keys on the nanoparticle surface, even though these keys only weakly interact with the nonmatching locks on normal cells, these weak, off-target interactions may still provide enough adhesion energy for the nanoparticles to penetrate the cell membrane and kill the healthy cells."

On the other hand, if the adhesion energy is not high enough, the nanoparticle won't get into the cell.

In "Mechanotargeting: Mechanics-dependent Cellular Uptake of Nanoparticles," published online ahead of print in the journal Advanced Materials, Zhang and the team report the results of experiments on cancer cells grown on hydrogels of variable stiffness. On soft hydrogels the cells remained cohesive and benign and experienced a nearly constant stress that limited the uptake of the nanoparticles. But on stiff hydrogels the cells became metastatic and adopted a three-dimensional shape, offering more surface area for nanoparticles to adhere, and became less stressed. Under this condition, the cells took up five times the number of nanoparticles as the benign cells.

"The nanoparticles are fluorescent, so we count the number of nanoparticles that get into the cell by the fluorescence intensity. We found that in the malignant cells the intensity is five times higher," Zhang said. "That proves that mechanotargeting works."

###

First author on the Advanced Materials paper is Qiong Wei, a doctoral student in Zhang's group. Other coauthors are former doctoral students Changjin Huang and Yao Zhang, and current doctoral students Tiankai Zhao and Peng Zhao, also in Zhang's group. Peter Butler, professor of biomedical engineering, Penn State, also contributed.

Support for this work was provided by the National Science Foundation and a National Institutes of Health grant to Butler and Zhang.

Media Contact

Walt Mills
wem12@psu.edu
814-865-0285

 @penn_state

http://live.psu.edu 

Walt Mills | EurekAlert!
Further information:
http://dx.doi.org/10.1002/adma.201707464

More articles from Health and Medicine:

nachricht Researchers find new potential approach to type 2 diabetes treatment
11.11.2019 | Weill Cornell Medicine

nachricht Why beta-blockers cause skin inflammation
07.11.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New Pitt research finds carbon nanotubes show a love/hate relationship with water

Carbon nanotubes (CNTs) are valuable for a wide variety of applications. Made of graphene sheets rolled into tubes 10,000 times smaller than a human hair, CNTs have an exceptional strength-to-mass ratio and excellent thermal and electrical properties. These features make them ideal for a range of applications, including supercapacitors, interconnects, adhesives, particle trapping and structural color.

New research reveals even more potential for CNTs: as a coating, they can both repel and hold water in place, a useful property for applications like printing,...

Im Focus: Magnets for the second dimension

If you've ever tried to put several really strong, small cube magnets right next to each other on a magnetic board, you'll know that you just can't do it. What happens is that the magnets always arrange themselves in a column sticking out vertically from the magnetic board. Moreover, it's almost impossible to join several rows of these magnets together to form a flat surface. That's because magnets are dipolar. Equal poles repel each other, with the north pole of one magnet always attaching itself to the south pole of another and vice versa. This explains why they form a column with all the magnets aligned the same way.

Now, scientists at ETH Zurich have managed to create magnetic building blocks in the shape of cubes that - for the first time ever - can be joined together to...

Im Focus: A new quantum data classification protocol brings us nearer to a future 'quantum internet'

The algorithm represents a first step in the automated learning of quantum information networks

Quantum-based communication and computation technologies promise unprecedented applications, such as unconditionally secure communications, ultra-precise...

Im Focus: Distorted Atoms

In two experiments performed at the free-electron laser FLASH in Hamburg a cooperation led by physicists from the Heidelberg Max Planck Institute for Nuclear physics (MPIK) demonstrated strongly-driven nonlinear interaction of ultrashort extreme-ultraviolet (XUV) laser pulses with atoms and ions. The powerful excitation of an electron pair in helium was found to compete with the ultrafast decay, which temporarily may even lead to population inversion. Resonant transitions in doubly charged neon ions were shifted in energy, and observed by XUV-XUV pump-probe transient absorption spectroscopy.

An international team led by physicists from the MPIK reports on new results for efficient two-electron excitations in helium driven by strong and ultrashort...

Im Focus: A Memory Effect at Single-Atom Level

An international research group has observed new quantum properties on an artificial giant atom and has now published its results in the high-ranking journal Nature Physics. The quantum system under investigation apparently has a memory - a new finding that could be used to build a quantum computer.

The research group, consisting of German, Swedish and Indian scientists, has investigated an artificial quantum system and found new properties.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

High entropy alloys for hot turbines and tireless metal-forming presses

05.11.2019 | Event News

Smart lasers open up new applications and are the “tool of choice” in digitalization

30.10.2019 | Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

 
Latest News

Magnetic tuning at the nanoscale

13.11.2019 | Physics and Astronomy

At future Mars landing spot, scientists spy mineral that could preserve signs of past life

13.11.2019 | Physics and Astronomy

Necessity is the mother of invention: Fraunhofer WKI tests utilization of low-value hardwood for wood fiberboard

13.11.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>