---
_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'
...
---
_id: '64884'
abstract:
- lang: eng
text: "To address the challenges associated with poor drug solubility and uncontrolled
drug release in conventional dosage forms, a combination of polymer design and
advanced drug delivery approaches has been employed. The development of pH-responsive
nanoparticles for controlled and selective drug release represents a notable advance
in adaptive nanomedicine. This study explores the design of a pH-responsive polymer,
poly(1,4-phenyleneacetone dimethylene ketal) (PPADK). Additionally, the incorporation
of light-responsive ortho-nitrobenzyl groups (o-NB-PPADK) enhanced the degradation
upon exposure to light. Based on the polymer, nanoparticles were prepared using
the solvent displacement method. The fluorescence dye Lumogen® Red was incorporated
as a model substance. The nanoparticles were characterized by dynamic light scattering
to determine their hydrodynamic diameter and size distribution, and the surface
charge was analyzed. Atomic force microscopy was used to visualize the surface
morphology. The nanoparticles remained stable under physiological pH conditions
while exhibiting accelerated degradation and substance release in acidic environment,
a property potentially exploitable for tumor targeting. Further enhanced degradation
and correspondingly increased release was achieved by incorporating light-responsive
elements in the polymer structure.\r\nThe cytotoxicity of these newly designed
nanoparticles was evaluated in cell culture using a breast cancer cell line. These
results support the potential of o-NB-PPADK nanoparticles as a possible candidate
for selective and effective cancer therapy, combining stimuli-responsive degradation
mechanisms for improved therapeutic outcomes."
article_number: '126127'
article_type: original
author:
- first_name: Maurice
full_name: Kramer, Maurice
last_name: Kramer
- first_name: Matthias
full_name: van der Linde, Matthias
last_name: van der Linde
- first_name: Lisa
full_name: Hönscheid, Lisa
last_name: Hönscheid
- 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, Dennis
last_name: Mulac
- 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, van der Linde M, Hönscheid L, et al. Enlightening release strategies:
Accelerated nanoparticle degradation and substance release utilizing light- and
pH-responsive polymers. International Journal of Pharmaceutics. 2025;684.
doi:10.1016/j.ijpharm.2025.126127'
apa: 'Kramer, M., van der Linde, M., Hönscheid, L., Horky, C., Völlmecke, K., Mulac,
D., Herrmann, F., Kuckling, D., & Langer, K. (2025). Enlightening release
strategies: Accelerated nanoparticle degradation and substance release utilizing
light- and pH-responsive polymers. International Journal of Pharmaceutics,
684, Article 126127. https://doi.org/10.1016/j.ijpharm.2025.126127'
bibtex: '@article{Kramer_van der Linde_Hönscheid_Horky_Völlmecke_Mulac_Herrmann_Kuckling_Langer_2025,
title={Enlightening release strategies: Accelerated nanoparticle degradation and
substance release utilizing light- and pH-responsive polymers}, volume={684},
DOI={10.1016/j.ijpharm.2025.126127},
number={126127}, journal={International Journal of Pharmaceutics}, publisher={Elsevier
BV}, author={Kramer, Maurice and van der Linde, Matthias and Hönscheid, Lisa and
Horky, Corinna and Völlmecke, Katharina and Mulac, Dennis and Herrmann, Fabian
and Kuckling, Dirk and Langer, Klaus}, year={2025} }'
chicago: 'Kramer, Maurice, Matthias van der Linde, Lisa Hönscheid, Corinna Horky,
Katharina Völlmecke, Dennis Mulac, Fabian Herrmann, Dirk Kuckling, and Klaus Langer.
“Enlightening Release Strategies: Accelerated Nanoparticle Degradation and Substance
Release Utilizing Light- and PH-Responsive Polymers.” International Journal
of Pharmaceutics 684 (2025). https://doi.org/10.1016/j.ijpharm.2025.126127.'
ieee: 'M. Kramer et al., “Enlightening release strategies: Accelerated nanoparticle
degradation and substance release utilizing light- and pH-responsive polymers,”
International Journal of Pharmaceutics, vol. 684, Art. no. 126127, 2025,
doi: 10.1016/j.ijpharm.2025.126127.'
mla: 'Kramer, Maurice, et al. “Enlightening Release Strategies: Accelerated Nanoparticle
Degradation and Substance Release Utilizing Light- and PH-Responsive Polymers.”
International Journal of Pharmaceutics, vol. 684, 126127, Elsevier BV,
2025, doi:10.1016/j.ijpharm.2025.126127.'
short: M. Kramer, M. van der Linde, L. Hönscheid, C. Horky, K. Völlmecke, D. Mulac,
F. Herrmann, D. Kuckling, K. Langer, International Journal of Pharmaceutics 684
(2025).
date_created: 2026-03-11T08:46:17Z
date_updated: 2026-03-11T08:52:22Z
department:
- _id: '163'
doi: 10.1016/j.ijpharm.2025.126127
intvolume: ' 684'
keyword:
- Nanoparticles
- Drug delivery
- Controlled release
- Stimuli-responsiveTumor targeting
language:
- iso: eng
main_file_link:
- url: https://www.sciencedirect.com/science/article/pii/S0378517325009640?via%3Dihub
publication: International Journal of Pharmaceutics
publication_identifier:
issn:
- 0378-5173
publication_status: published
publisher: Elsevier BV
status: public
title: 'Enlightening release strategies: Accelerated nanoparticle degradation and
substance release utilizing light- and pH-responsive polymers'
type: journal_article
user_id: '94'
volume: 684
year: '2025'
...
---
_id: '30927'
article_number: '6081'
author:
- first_name: Berthold
full_name: Reis, Berthold
last_name: Reis
- first_name: David
full_name: Vehlow, David
last_name: Vehlow
- first_name: Tarik
full_name: Rust, Tarik
last_name: Rust
- first_name: Dirk
full_name: Kuckling, Dirk
id: '287'
last_name: Kuckling
- first_name: Martin
full_name: Müller, Martin
last_name: Müller
citation:
ama: Reis B, Vehlow D, Rust T, Kuckling D, Müller M. Thermoresponsive Catechol Based-Polyelectrolyte
Complex Coatings for Controlled Release of Bortezomib. International Journal
of Molecular Science. 2019;20(23). doi:10.3390/ijms20236081
apa: Reis, B., Vehlow, D., Rust, T., Kuckling, D., & Müller, M. (2019). Thermoresponsive
Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib.
International Journal of Molecular Science, 20(23), Article 6081.
https://doi.org/10.3390/ijms20236081
bibtex: '@article{Reis_Vehlow_Rust_Kuckling_Müller_2019, title={Thermoresponsive
Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib},
volume={20}, DOI={10.3390/ijms20236081},
number={236081}, journal={International Journal of Molecular Science}, publisher={MDPI},
author={Reis, Berthold and Vehlow, David and Rust, Tarik and Kuckling, Dirk and
Müller, Martin}, year={2019} }'
chicago: Reis, Berthold, David Vehlow, Tarik Rust, Dirk Kuckling, and Martin Müller.
“Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled
Release of Bortezomib.” International Journal of Molecular Science 20,
no. 23 (2019). https://doi.org/10.3390/ijms20236081.
ieee: 'B. Reis, D. Vehlow, T. Rust, D. Kuckling, and M. Müller, “Thermoresponsive
Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib,”
International Journal of Molecular Science, vol. 20, no. 23, Art. no. 6081,
2019, doi: 10.3390/ijms20236081.'
mla: Reis, Berthold, et al. “Thermoresponsive Catechol Based-Polyelectrolyte Complex
Coatings for Controlled Release of Bortezomib.” International Journal of Molecular
Science, vol. 20, no. 23, 6081, MDPI, 2019, doi:10.3390/ijms20236081.
short: B. Reis, D. Vehlow, T. Rust, D. Kuckling, M. Müller, International Journal
of Molecular Science 20 (2019).
date_created: 2022-04-21T09:00:09Z
date_updated: 2022-04-21T09:00:31Z
department:
- _id: '311'
doi: 10.3390/ijms20236081
intvolume: ' 20'
issue: '23'
keyword:
- catechol chemistry
- poly(caffeic acid)
- polyelectrolyte complex coatings
- thermoresponsive coatings
- controlled release
- bortezomib
- multiple myeloma
language:
- iso: eng
publication: International Journal of Molecular Science
publication_status: published
publisher: MDPI
status: public
title: Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled
Release of Bortezomib
type: journal_article
user_id: '94'
volume: 20
year: '2019'
...