While there are many types of drug ferrying nanoparticles already in existence and more under development, in order for them to be safe and effective in clinical practice they have to be uniformly manufacturable. Different sizes and shapes of nanoparticles can lead to inconsistent results. This can muddy studies and clinical results. Now researchers at Johannes Gutenberg University Mainz in Germany and University of Tokyo in Japan are reporting in the venerable journal Angewandte Chemie on a new method of producing nanoparticles uniformly, while giving scientists and engineers the ability to carefully control nano shape and function.
The investigators used reactive polypept(o)ides (polysarcosine-block-polypeptide copolymers) as the main ingredient to create carefully realized nanoparticles. This unusual material is resistant to reactions with proteins, exhibits high water-solubilty of polysarcosine, responds to external stimuli, and can be shaped in different ways.
Some details according to Johannes Gutenberg University Mainz:
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, 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, [a leader of the research team].
Study in journal Angewandte Chemie: Secondary-Structure-Driven Self-Assembly of Reactive Polypept(o)ides: Controlling Size, Shape, and Function of Core Cross-Linked Nanostructures…
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