Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Multifunctional nano-sized drug carriers based on reactive polypept(o)ides

13.09.2017

In cooperation with researchers from the University of Tokyo and Gutenberg Research Awardee Prof. Kazunori Kataoka, Chemists from Mainz have been able to demonstrate that reactive polypept(o)ides constitute ideal building blocks to control morphology and function of carrier systems in a simple but precise manner.

Nano-sized carrier systems find medical application to improve pharmacologic properties of bioactive agents. For many therapeutic approaches, it is important that the carrier system can stably incorporate the cargo during circulation without inducing aggregation, while cargo should ideally only be released after successful cellular uptake.


Secondary structure formation enables morphology control while reactive groups in the polypeptide segment allow for adjustment of function.

ill./©:Kristina Klinker/Olga Schäfer

These requirements have thus far only been met by chemistry approaches with nanoparticles that are difficult to characterize. Consequently, clinical translation of these systems has been very difficult to achieve.

In cooperation with researchers from the University of Tokyo and Gutenberg Research Awardee Prof. Kazunori Kataoka, Chemists from Mainz have been able to demonstrate that reactive polypept(o)ides constitute ideal building blocks to control morphology and function of carrier systems in a simple but precise manner.

Polypept(o)ides (polysarcosine-block-polypeptide copolymers) have emerged as interesting hybrid materials for drug carrier systems since they combine protein-resistance and high water-solubilty of polysarcosine with the stimuli-responsiveness, intrinsic multifunctionality, and secondary structure formation of polypeptides.

In this cooperative work, the researchers could show for the first time that the formation of β-sheets by the synthetic polypeptide segment can be exploited to deliberately manipulate the morphology of polymeric micelles (Klinker K et al. Angew. Chem. Int. Ed. 2017, 56 (32), 9608-9613 & Angew. Chem. 2017, 129 (32), 9737–9742), which enables the synthesis of either spherical or worm-like micelles from the same block copolymer.

By employing reactive groups in the polypeptide segment of the block copolymer, micelles can be core cross-linked by dithiols, resulting in bio-reversible disulfide bonds. Due a difference in redox potential, disulfides are considered stable extracellularly, while they are rapidly reduced to free dithiols intracellularly, which leads to a disintegration of the carrier system and release of the cargo.

“In this way, a variety of different nanocarriers with different functions becomes readily accessible from one single block copolymer and a very selective post-polymerization step. This modular approach to nanoparticles with different function and morphology bears the advantage to address important questions with good comparability, such as the influence of size and shape on in vivo circulation times, biodistribution, tumor accumulation, cell uptake and therapeutic response since the same starting material is used” comments Matthias Barz.

First in vivo experiments have already demonstrated that these core-stabilized micellar nanocarriers exhibit stable circulation behavior, thus indicating that interactions with serum components or blood vessels are absent. Only by ensuring that no unspecific interactions occur within the complex biological setting, cellular uptake in desired specific cell populations seems feasible. The therapeutic potential of the described nanoparticle platform will be further investigated with regards to immunotherapy of malignant melanoma within the SFB 1066.

Image:
http://www.uni-mainz.de/bilder_presse/09_orgchemie_nanodimensionale_wirkstofftra...
Secondary structure formation enables morphology control while reactive groups in the polypeptide segment allow for adjustment of function.
ill./©:Kristina Klinker/Olga Schäfer

Publication:
Klinker K, Schäfer O, Huesmann D, Bauer T, Capelôa L, Braun L, Stergiou N, Schinnerer M, Dirisala A, Miyata K, Osada K, Cabral H, Kataoka K, Barz M*.
Secondary Structure-Driven Self-Assembly of Reactive Polypept(o)ides: Controlling Size, Shape and Function of Core Cross-Linked Nanostructures.
Angew. Chem. Int. Ed. 2017, 56 (32), 9608-9613
Sekundärstrukturausbildung als Triebkraft für die Selbstassemblierung von reaktiven Polypept(o)iden: Steuerung von Größe, Form und Funktion von kernvernetzten Nanostrukturen.
Angew. Chem. 2017, 129 (32), 9737–9742

Further information:
Dr. Matthias Barz
Institute of Organic Chemistry
Johannes Gutenberg University Mainz
55099 Mainz, GERMANY
phone +49 6131 39-26256
fax +49 6131 39-26092
e-mail: barz@uni-mainz.de

Weitere Informationen:

http://www.ak-zentel.chemie.uni-mainz.de

Petra Giegerich | idw - Informationsdienst Wissenschaft
Further information:
http://www.fau.de/

More articles from Life Sciences:

nachricht Supported liquid metal catalysts – a new generation of reaction accelerators
13.09.2017 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht Radioactive Metal Complexes for Tumour Diagnosis and Therapy
12.09.2017 | Universität Heidelberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

Im Focus: Artificial Enzymes for Hydrogen Conversion

Scientists from the MPI for Chemical Energy Conversion report in the first issue of the new journal JOULE.

Cell Press has just released the first issue of Joule, a new journal dedicated to sustainable energy research. In this issue James Birrell, Olaf Rüdiger,...

Im Focus: Using Mirrors to Improve the Quality of Light Particles

Scientists from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute have succeeded in dramatically improving the quality of individual photons generated by a quantum system. The scientists have successfully put a 10-year-old theoretical prediction into practice. With their paper, published recently in Physical Review X, they have taken an important step towards future applications in quantum information technology.

For a number of years, scientists have been working on using electron spins to store and process information. A possible approach is to use a quantum system in...

Im Focus: High-speed Quantum Memory for Photons

Physicists from the University of Basel have developed a memory that can store photons. These quantum particles travel at the speed of light and are thus suitable for high-speed data transfer. The researchers were able to store them in an atomic vapor and read them out again later without altering their quantum mechanical properties too much. This memory technology is simple and fast and it could find application in a future quantum Internet. The journal Physical Review Letters has published the results.

Even today, fast data transfer in telecommunication networks employs short light pulses. Ultra broadband technology uses optical fiber links through which...

Im Focus: Discovery of the most accelerated binary pulsar

Fifty years after Jocelyn Bell discovered the first pulsar, students are no longer going through reams of paper from pen chart recorders but instead search through 1,000s of terabytes of data to find these enigmatic pulsating radio stars. The most extreme binary pulsar system so far, with accelerations of up to 70 g has been discovered by researchers at the Max Planck Institute for Radio Astronomy (MPIfR) in Bonn. At their closest approach the orbit of the pulsar and its companion neutron star would easily fit inside the radius of the Sun.

Although most of the more than 2,500 pulsars known are solitary objects, a few are found in tight binary systems. The discovery of the first of these, the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

IVAM’s LaserForum visits the Swiss canton of St. Gallen with the topic ultrashort pulse lasers

06.09.2017 | Event News

 
Latest News

Supported liquid metal catalysts – a new generation of reaction accelerators

13.09.2017 | Life Sciences

Multifunctional nano-sized drug carriers based on reactive polypept(o)ides

13.09.2017 | Life Sciences

Radioactive Metal Complexes for Tumour Diagnosis and Therapy

12.09.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>