Versatile sperm-micromotors for targeted drug delivery

Datum

20.08.2019

Zeit

10:00 - 11:00

Sprecher

Haifeng Xu

Zugehörigkeit

Institut für Integrative Nanowissenschaften (IIN)

Sprache

en

Hauptthema

Materialien

Host

Kristina Krummer-Meier

Beschreibung

Micromotors are attracting a lot of attention as they represent the new generation of targeted drug delivery systems. In particular, micromotors based on motile cells and/or organisms are promising due to their adaptability in complex physiological media, their interaction with other biological entities and their drug encapsulation possibilities. In particular, our group has been pioneer in the development and application of sperm-based micromotors, mainly to address male infertility problems.To expand the application range of sperm-based micromotors, here we propose their use as targeted drug delivery systems, in particular to treat gynecological cancers. For that, we loaded an anti-cancer drug into bull sperms and evaluated their motility after loading as well as their killing efficiency against cervical cancer cells. We also designed a magnetic scaffold called tetrapod for single sperm guidance and release, showing the targeting of the proposed system. However, questions still remain. The first one is: can we transfer this concept to human material and treat more relevant cancer tissue (e.g. ex-vivo cancer tumors from the ovary)? To answer this question, we applied a similar protocol to load drugs into human sperms. We could verify the loading efficiency as well as the precise location of drug within the sperm, using high resolution microscopy. We employed human sperm-micromotors to treat ovarian cancer cells which are originated in the oviduct before being spread to the ovary. Given the interspecific difference between human and other mammalian sperms, as well as the difference between primary and over-passaged cells, this is the first micro-robotic system employing human sperms towards early tumor lesions treatment. Another raised question was: can such sperm-hybrid micromotor swim in fluids different from the ones found in the reproductive system? In particular, blood is one of the most important body fluids as it is the most commonly used drug delivery route. However it is a very harsh environment, considering the high complexity of blood and the high flow rates. For that we took advantage of the sperm rheotaxis to create a blood-adapted sperm-micromotor with anti-coagulant properties. The caps of such bio-hybrids were loaded with heparin-filled liposomes, showing a significant anticoagulation effect compared to the control samples. The final question was: is there any way we can control the effective drug dose of such systems? One alternative we propose here is to transport multiple sperms and/or multiple cargoes. In this regard, we developed a train-like sperm-micromotor which consists in a self-assembly of multiple sperm-micromotors. The slender configuration enabled it to adapt in narrow channels and fluid flows. Then the sperms can be released by an abrupt change of the magnetic field orientation, being able to transport and release ca. 10 sperms at once. We believe this research represents a great breakthrough in the micro-robotic based drug delivery field and inspires the application of sperm-hybrid micromotors in a variety of realistic body environments.

Links

• Seminars at the IFW

Letztmalig verändert: 20.08.2019, 00:08:20