---
_id: '65659'
abstract:
- lang: eng
text: Over the past decades, nanoparticulate drug carrier systems have emerged as
promising tools in medicine. A persistent challenge in current pharmacotherapy
is the limited selectivity of active pharmaceutical ingredients, resulting in
undesirable side effects. Smart drug delivery systems, which release encapsulated
active pharmaceutical ingredients in response to specific stimuli, offer a potential
solution by enabling controlled drug release. This approach can be particularly
relevant for exploiting biochemical differences between extracellular and intracellular
environments. In this study, self-immolative polydisulfide based polymers manufactured
from dithiothreitol were processed into nanoparticle formulations to respond preferentially
to elevated glutathione levels, which are characteristic of intracellular environments
and are often increased in tumor cells. The influence of polymer chain length
on the physicochemical properties of the resulting nanoparticles was investigated.
Lumogen® Red was incorporated as a model substance to determine the loading capacity
of the carrier system. Degradation was characterized using dynamic light scattering
and asymmetric flow field-flow fractionation, as well as by imaging techniques
such as atomic force microscopy. Selective release of the embedded substance was
demonstrated at elevated glutathione concentrations, while no significant release
was observed at extracellularly relevant levels (10 µM glutathione), where the
behavior was comparable to the buffer control. Increased release was observed
under intracellularly relevant conditions (2 – 10 mM glutathione). These findings
support a redox-responsive behavior under intracellular-like conditions. The latter
was proven for primary fibroblasts and the cancer cell lines BT-474, MCF-7 and
SK-BR-3 by quantification of intracellular low molecular weight thiols. The nanoparticle
uptake was confirmed in the investigated cell lines by visualization via confocal
laser scanning microscopy. Via lysosomal staining it was shown that nanoparticles
accumulate in lysosomes. Furthermore, the carrier system itself showed no cytotoxic
properties in cell culture studies against the four different cell types. The
developed system is a suitable and very promising smart drug delivery system in
the context of controlled drug release.
article_number: '100510'
article_type: original
author:
- first_name: Maurice
full_name: Kramer, Maurice
last_name: Kramer
- first_name: Corinna
full_name: Horky, Corinna
last_name: Horky
- first_name: Katharina
full_name: Völlmecke, Katharina
last_name: Völlmecke
- first_name: Dennis
full_name: Mulac-Hahnen, Dennis
last_name: Mulac-Hahnen
- first_name: Fabian
full_name: Herrmann, Fabian
last_name: Herrmann
- first_name: Dirk
full_name: Kuckling, Dirk
id: '287'
last_name: Kuckling
- first_name: Klaus
full_name: Langer, Klaus
last_name: Langer
citation:
ama: 'Kramer M, Horky C, Völlmecke K, et al. Smart drug delivery systems for potential
targeted cancer therapy: Exploiting increased glutathione levels in tumor microenvironments.
Next Nanotechnology. 2026;9. doi:10.1016/j.nxnano.2026.100510'
apa: 'Kramer, M., Horky, C., Völlmecke, K., Mulac-Hahnen, D., Herrmann, F., Kuckling,
D., & Langer, K. (2026). Smart drug delivery systems for potential targeted
cancer therapy: Exploiting increased glutathione levels in tumor microenvironments.
Next Nanotechnology, 9, Article 100510. https://doi.org/10.1016/j.nxnano.2026.100510'
bibtex: '@article{Kramer_Horky_Völlmecke_Mulac-Hahnen_Herrmann_Kuckling_Langer_2026,
title={Smart drug delivery systems for potential targeted cancer therapy: Exploiting
increased glutathione levels in tumor microenvironments}, volume={9}, DOI={10.1016/j.nxnano.2026.100510},
number={100510}, journal={Next Nanotechnology}, publisher={Elsevier BV}, author={Kramer,
Maurice and Horky, Corinna and Völlmecke, Katharina and Mulac-Hahnen, Dennis and
Herrmann, Fabian and Kuckling, Dirk and Langer, Klaus}, year={2026} }'
chicago: 'Kramer, Maurice, Corinna Horky, Katharina Völlmecke, Dennis Mulac-Hahnen,
Fabian Herrmann, Dirk Kuckling, and Klaus Langer. “Smart Drug Delivery Systems
for Potential Targeted Cancer Therapy: Exploiting Increased Glutathione Levels
in Tumor Microenvironments.” Next Nanotechnology 9 (2026). https://doi.org/10.1016/j.nxnano.2026.100510.'
ieee: 'M. Kramer et al., “Smart drug delivery systems for potential targeted
cancer therapy: Exploiting increased glutathione levels in tumor microenvironments,”
Next Nanotechnology, vol. 9, Art. no. 100510, 2026, doi: 10.1016/j.nxnano.2026.100510.'
mla: 'Kramer, Maurice, et al. “Smart Drug Delivery Systems for Potential Targeted
Cancer Therapy: Exploiting Increased Glutathione Levels in Tumor Microenvironments.”
Next Nanotechnology, vol. 9, 100510, Elsevier BV, 2026, doi:10.1016/j.nxnano.2026.100510.'
short: M. Kramer, C. Horky, K. Völlmecke, D. Mulac-Hahnen, F. Herrmann, D. Kuckling,
K. Langer, Next Nanotechnology 9 (2026).
date_created: 2026-05-20T08:37:30Z
date_updated: 2026-05-20T08:41:56Z
department:
- _id: '163'
doi: 10.1016/j.nxnano.2026.100510
intvolume: ' 9'
keyword:
- Nanoparticles
- Smart drug delivery
- Controlled release
- Self-immolative polymers
- Tumor targeting
language:
- iso: eng
main_file_link:
- url: https://www.sciencedirect.com/science/article/pii/S294982952600149X?via%3Dihub
publication: Next Nanotechnology
publication_identifier:
issn:
- 2949-8295
publication_status: published
publisher: Elsevier BV
status: public
title: 'Smart drug delivery systems for potential targeted cancer therapy: Exploiting
increased glutathione levels in tumor microenvironments'
type: journal_article
user_id: '94'
volume: 9
year: '2026'
...