Sperm as a drug carrier: multi-sperm transport and propulsion force measurement

Date

Nov 16, 2017

Time

10:00 AM - 11:00 AM

Speaker

Haifeng Xu

Affiliation

Institut für Integrative Nanowissenschaften (IIN)

Language

en

Main Topic

Materialien

Other Topics

Materialien, Physik

Host

Kristina Krummer-Meier

Description

The sperm, as a combination of a naturally selected micromotor and cellular drug carrier, shows a great potential on drug delivery to treat diseases in the female reproductive tract. Owing to its crystalline nucleus1 and compact membrane system, the sperm can encapsulate high amount of drug and protect it from body fluid dilution. After a precise guidance with a specific magnetic structure, the sperm can release drug and enhance the transfer of it into cancer cells relying on its cell-fusion ability.2 In previous work, we showed the successful loading of BSA into sperms and fabrication of tetrapod-like structures, as well as the sperm release when hitting PDMS walls and HeLa cells by mechanical deformation of tetrapod arms. Here, we present the completion and improvement of the study of sperm-tetrapod micromotor for the delivery of DOX-HCl (doxorubicin hydrochloride, anticancer drug). The sperm exhibited an impressive encapsulation capability of DOX-HCl, carrying an amount of ca. 15 pg of drug in one sperm. No significant difference was found on sperm motility between DOX-HCl-loaded sperms and unloaded sperms, making them sufficiently active for subsequent transport. Besides, DOX-HCl-loaded sperms showed a more efficient cell-killing effect on HeLa spheroids compared to DOX-HCl solution with the same amount of drug. To demonstrate the potential application of this system on targeted drug delivery, DOX-HCl-loaded sperms were coupled in tetrapods and guided to HeLa spheroids. Fluorescence spreading indicated the drug distribution from sperm to HeLa cells (Fig. 1a), leading to the cancer cell apoptosis. SEM images confirmed the drug effect on a cancer cell by a fused drug-loaded sperm. Despite the experimental achievement in vitro, there are still several challenges to apply this in vivo, such as real-time imaging, biodegradability and effective drug dose. Thus, we propose a multi-sperm transport system (Fig. 1b) by using hyaluronic acid (HA) micro-beads as a sperm attraction platform to improve the drug dose by capturing multiple sperms. Preliminary results showed that HA micro-beads could efficiently attract multiple sperms and be delivered to a target by using a big magnetic helical transporter. After that, sperms were able to escape due to the slow dissolution of HA. This development brought us a promising strategy to enhance the effective drug dose. In addition, we suggest a force-measurement device (Fig. 1c) to evaluate the propulsion power of the sperm for a better understanding on its cumulus cells or tissue penetration ability. We believe that this novel approach of using sperm-hybrid micromotors as drug carriers will represent a great breakthrough in the treatment of gynecological cancers in the future. References: 1. Johnson, G. D.; Lalancette, C.; Linnemann, A. K.; Leduc, F.; Boissonneault, G.; Krawetz, S. A., The sperm nucleus: chromatin, RNA, and the nuclear matrix. Reproduction 2011, 141, 21-36. 2. Mattioli, M.; Gloria, A.; Mauro, A.; Gioia, L.; Barboni, B., Fusion as the result of sperm-somatic cell interaction. Reproduction 2009, 138, 679-87.

Links

• Seminars at the IFW

Last modified: Nov 16, 2017, 8:55:09 AM