Imaging the intracellular degradation of biodegradable polymer nanoparticles.
In recent years, the development of smart drug delivery systems based on biodegradable polymeric nanoparticles has become of great interest. Drug-loaded nanoparticles can be introduced into the cell interior via endocytotic processes followed by the slow release of the drug due to degradation of the nanoparticle. In this work, poly(L-lactic acid) (PLLA) was chosen as the biodegradable polymer. Although common degradation of PLLA has been studied in various biological environments, intracellular degradation processes have been examined only to a very limited extent. PLLA nanoparticles with an average diameter of approximately 120 nm were decorated with magnetite nanocrystals and introduced into mesenchymal stem cells (MSCs). The release of the magnetite particles from the surface of the PLLA nanoparticles during the intracellular residence was monitored by transmission electron microscopy (TEM) over a period of 14 days. It was demonstrated by the release of the magnetite nanocrystals from the PLLA surface that the PLLA nanoparticles do in fact undergo degradation within the cell. Furthermore, even after 14 days of residence, the PLLA nanoparticles were found in the MSCs. Additionally, the ultrastructural TEM examinations yield insight into the long term intercellular fate of these nanoparticles. From the statistical analysis of ultrastructural details (e.g., number of detached magnetite crystals, and the number of nanoparticles in one endosome), we demonstrate the importance of TEM studies for such applications in addition to fluorescence studies (flow cytometry and confocal laser scanning microscopy).
Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55123 Mainz, Germany.
Anne-Kathrin
AK
Barthel
Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55123 Mainz, Germany.
Martin
M
Dass
Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55123 Mainz, Germany.
Melanie
M
Dröge
Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55123 Mainz, Germany.
Jens-Michael
JM
Cramer
Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55123 Mainz, Germany.
Daniela
D
Baumann
Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55123 Mainz, Germany.
Markus
M
Urban
Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55123 Mainz, Germany.
Katharina
K
Landfester
Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55123 Mainz, Germany ; 3rd Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
Volker
V
Mailänder
Max-Planck-Institute for Polymer Research, Ackermannweg 10, 55123 Mainz, Germany.
Ingo
I
Lieberwirth
PLLA nanoparticles; biodegradation; mesenchymal stem cells; transmission electron microscopy