[{"main_file_link":[{"url":"https://www.sciencedirect.com/science/article/pii/S294982952600149X?via%3Dihub"}],"article_number":"100510","language":[{"iso":"eng"}],"doi":"10.1016/j.nxnano.2026.100510","title":"Smart drug delivery systems for potential targeted cancer therapy: Exploiting increased glutathione levels in tumor microenvironments","year":"2026","publication_identifier":{"issn":["2949-8295"]},"author":[{"full_name":"Kramer, Maurice","first_name":"Maurice","last_name":"Kramer"},{"full_name":"Horky, Corinna","last_name":"Horky","first_name":"Corinna"},{"first_name":"Katharina","last_name":"Völlmecke","full_name":"Völlmecke, Katharina"},{"full_name":"Mulac-Hahnen, Dennis","first_name":"Dennis","last_name":"Mulac-Hahnen"},{"full_name":"Herrmann, Fabian","last_name":"Herrmann","first_name":"Fabian"},{"full_name":"Kuckling, Dirk","last_name":"Kuckling","first_name":"Dirk","id":"287"},{"full_name":"Langer, Klaus","first_name":"Klaus","last_name":"Langer"}],"date_updated":"2026-05-20T08:41:56Z","publication_status":"published","intvolume":"         9","article_type":"original","date_created":"2026-05-20T08:37:30Z","keyword":["Nanoparticles","Smart drug delivery","Controlled release","Self-immolative polymers","Tumor targeting"],"type":"journal_article","department":[{"_id":"163"}],"publication":"Next Nanotechnology","abstract":[{"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.","lang":"eng"}],"publisher":"Elsevier BV","_id":"65659","user_id":"94","volume":9,"status":"public","citation":{"mla":"Kramer, Maurice, et al. “Smart Drug Delivery Systems for Potential Targeted Cancer Therapy: Exploiting Increased Glutathione Levels in Tumor Microenvironments.” <i>Next Nanotechnology</i>, vol. 9, 100510, Elsevier BV, 2026, doi:<a href=\"https://doi.org/10.1016/j.nxnano.2026.100510\">10.1016/j.nxnano.2026.100510</a>.","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={<a href=\"https://doi.org/10.1016/j.nxnano.2026.100510\">10.1016/j.nxnano.2026.100510</a>}, 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} }","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. <i>Next Nanotechnology</i>. 2026;9. doi:<a href=\"https://doi.org/10.1016/j.nxnano.2026.100510\">10.1016/j.nxnano.2026.100510</a>","ieee":"M. Kramer <i>et al.</i>, “Smart drug delivery systems for potential targeted cancer therapy: Exploiting increased glutathione levels in tumor microenvironments,” <i>Next Nanotechnology</i>, vol. 9, Art. no. 100510, 2026, doi: <a href=\"https://doi.org/10.1016/j.nxnano.2026.100510\">10.1016/j.nxnano.2026.100510</a>.","apa":"Kramer, M., Horky, C., Völlmecke, K., Mulac-Hahnen, D., Herrmann, F., Kuckling, D., &#38; Langer, K. (2026). Smart drug delivery systems for potential targeted cancer therapy: Exploiting increased glutathione levels in tumor microenvironments. <i>Next Nanotechnology</i>, <i>9</i>, Article 100510. <a href=\"https://doi.org/10.1016/j.nxnano.2026.100510\">https://doi.org/10.1016/j.nxnano.2026.100510</a>","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.” <i>Next Nanotechnology</i> 9 (2026). <a href=\"https://doi.org/10.1016/j.nxnano.2026.100510\">https://doi.org/10.1016/j.nxnano.2026.100510</a>.","short":"M. Kramer, C. Horky, K. Völlmecke, D. Mulac-Hahnen, F. Herrmann, D. Kuckling, K. Langer, Next Nanotechnology 9 (2026)."}},{"citation":{"ieee":"M. Kramer <i>et al.</i>, “Enlightening release strategies: Accelerated nanoparticle degradation and substance release utilizing light- and pH-responsive polymers,” <i>International Journal of Pharmaceutics</i>, vol. 684, Art. no. 126127, 2025, doi: <a href=\"https://doi.org/10.1016/j.ijpharm.2025.126127\">10.1016/j.ijpharm.2025.126127</a>.","apa":"Kramer, M., van der Linde, M., Hönscheid, L., Horky, C., Völlmecke, K., Mulac, D., Herrmann, F., Kuckling, D., &#38; Langer, K. (2025). Enlightening release strategies: Accelerated nanoparticle degradation and substance release utilizing light- and pH-responsive polymers. <i>International Journal of Pharmaceutics</i>, <i>684</i>, Article 126127. <a href=\"https://doi.org/10.1016/j.ijpharm.2025.126127\">https://doi.org/10.1016/j.ijpharm.2025.126127</a>","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.” <i>International Journal of Pharmaceutics</i> 684 (2025). <a href=\"https://doi.org/10.1016/j.ijpharm.2025.126127\">https://doi.org/10.1016/j.ijpharm.2025.126127</a>.","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).","mla":"Kramer, Maurice, et al. “Enlightening Release Strategies: Accelerated Nanoparticle Degradation and Substance Release Utilizing Light- and PH-Responsive Polymers.” <i>International Journal of Pharmaceutics</i>, vol. 684, 126127, Elsevier BV, 2025, doi:<a href=\"https://doi.org/10.1016/j.ijpharm.2025.126127\">10.1016/j.ijpharm.2025.126127</a>.","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={<a href=\"https://doi.org/10.1016/j.ijpharm.2025.126127\">10.1016/j.ijpharm.2025.126127</a>}, 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} }","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. <i>International Journal of Pharmaceutics</i>. 2025;684. doi:<a href=\"https://doi.org/10.1016/j.ijpharm.2025.126127\">10.1016/j.ijpharm.2025.126127</a>"},"volume":684,"user_id":"94","_id":"64884","publisher":"Elsevier BV","status":"public","department":[{"_id":"163"}],"type":"journal_article","keyword":["Nanoparticles","Drug delivery","Controlled release","Stimuli-responsiveTumor targeting"],"date_created":"2026-03-11T08:46:17Z","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."}],"publication":"International Journal of Pharmaceutics","doi":"10.1016/j.ijpharm.2025.126127","language":[{"iso":"eng"}],"main_file_link":[{"url":"https://www.sciencedirect.com/science/article/pii/S0378517325009640?via%3Dihub"}],"article_number":"126127","intvolume":"       684","article_type":"original","date_updated":"2026-03-11T08:52:22Z","publication_status":"published","author":[{"full_name":"Kramer, Maurice","first_name":"Maurice","last_name":"Kramer"},{"full_name":"van der Linde, Matthias","last_name":"van der Linde","first_name":"Matthias"},{"first_name":"Lisa","last_name":"Hönscheid","full_name":"Hönscheid, Lisa"},{"first_name":"Corinna","last_name":"Horky","full_name":"Horky, Corinna"},{"full_name":"Völlmecke, Katharina","first_name":"Katharina","last_name":"Völlmecke"},{"first_name":"Dennis","last_name":"Mulac","full_name":"Mulac, Dennis"},{"full_name":"Herrmann, Fabian","last_name":"Herrmann","first_name":"Fabian"},{"id":"287","full_name":"Kuckling, Dirk","last_name":"Kuckling","first_name":"Dirk"},{"full_name":"Langer, Klaus","first_name":"Klaus","last_name":"Langer"}],"publication_identifier":{"issn":["0378-5173"]},"year":"2025","title":"Enlightening release strategies: Accelerated nanoparticle degradation and substance release utilizing light- and pH-responsive polymers"},{"status":"public","_id":"30927","publisher":"MDPI","user_id":"94","volume":20,"citation":{"mla":"Reis, Berthold, et al. “Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib.” <i>International Journal of Molecular Science</i>, vol. 20, no. 23, 6081, MDPI, 2019, doi:<a href=\"https://doi.org/10.3390/ijms20236081\">10.3390/ijms20236081</a>.","apa":"Reis, B., Vehlow, D., Rust, T., Kuckling, D., &#38; Müller, M. (2019). Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib. <i>International Journal of Molecular Science</i>, <i>20</i>(23), Article 6081. <a href=\"https://doi.org/10.3390/ijms20236081\">https://doi.org/10.3390/ijms20236081</a>","ieee":"B. Reis, D. Vehlow, T. Rust, D. Kuckling, and M. Müller, “Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib,” <i>International Journal of Molecular Science</i>, vol. 20, no. 23, Art. no. 6081, 2019, doi: <a href=\"https://doi.org/10.3390/ijms20236081\">10.3390/ijms20236081</a>.","chicago":"Reis, Berthold, David Vehlow, Tarik Rust, Dirk Kuckling, and Martin Müller. “Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib.” <i>International Journal of Molecular Science</i> 20, no. 23 (2019). <a href=\"https://doi.org/10.3390/ijms20236081\">https://doi.org/10.3390/ijms20236081</a>.","ama":"Reis B, Vehlow D, Rust T, Kuckling D, Müller M. Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib. <i>International Journal of Molecular Science</i>. 2019;20(23). doi:<a href=\"https://doi.org/10.3390/ijms20236081\">10.3390/ijms20236081</a>","short":"B. Reis, D. Vehlow, T. Rust, D. Kuckling, M. Müller, International Journal of Molecular Science 20 (2019).","bibtex":"@article{Reis_Vehlow_Rust_Kuckling_Müller_2019, title={Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib}, volume={20}, DOI={<a href=\"https://doi.org/10.3390/ijms20236081\">10.3390/ijms20236081</a>}, 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} }"},"title":"Thermoresponsive Catechol Based-Polyelectrolyte Complex Coatings for Controlled Release of Bortezomib","year":"2019","author":[{"last_name":"Reis","first_name":"Berthold","full_name":"Reis, Berthold"},{"full_name":"Vehlow, David","first_name":"David","last_name":"Vehlow"},{"first_name":"Tarik","last_name":"Rust","full_name":"Rust, Tarik"},{"id":"287","last_name":"Kuckling","first_name":"Dirk","full_name":"Kuckling, Dirk"},{"full_name":"Müller, Martin","first_name":"Martin","last_name":"Müller"}],"date_updated":"2022-04-21T09:00:31Z","publication_status":"published","intvolume":"        20","article_number":"6081","language":[{"iso":"eng"}],"doi":"10.3390/ijms20236081","issue":"23","publication":"International Journal of Molecular Science","date_created":"2022-04-21T09:00:09Z","keyword":["catechol chemistry","poly(caffeic acid)","polyelectrolyte complex coatings","thermoresponsive coatings","controlled release","bortezomib","multiple myeloma"],"type":"journal_article","department":[{"_id":"311"}]}]