Potential of a CO2-Responsive supramolecular drug-carrier system as a safer and more effective treatment for cancer
We combined carbon dioxide (CO2)-responsive cytosine-containing rhodamine 6G (Cy-R6G) as a hydrophobic anticancer agent with hydrogen-bonded cytosine-functionalized polyethylene glycol (Cy-PEG) as a hydrophilic supramolecular carrier to construct a CO2-responsive drug delivery system, with the aim o...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-12-01
|
| Series: | Materials Today Bio |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424003806 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846123369132457984 |
|---|---|
| author | Enyew Alemayehu Bayle Fasih Bintang Ilhami Jem-Kun Chen Chih-Chia Cheng |
| author_facet | Enyew Alemayehu Bayle Fasih Bintang Ilhami Jem-Kun Chen Chih-Chia Cheng |
| author_sort | Enyew Alemayehu Bayle |
| collection | DOAJ |
| description | We combined carbon dioxide (CO2)-responsive cytosine-containing rhodamine 6G (Cy-R6G) as a hydrophobic anticancer agent with hydrogen-bonded cytosine-functionalized polyethylene glycol (Cy-PEG) as a hydrophilic supramolecular carrier to construct a CO2-responsive drug delivery system, with the aim of enhancing the responsiveness of the system to the tumor microenvironment and thus the overall effectiveness of anticancer therapy. Due to self-complementary hydrogen bonding interactions between cytosine units, Cy-R6G and Cy-PEG co-assemble in water to form spherical-like nanogels, with Cy-R6G effectively encapsulated within the nanogels. The nanogels exhibit several distinctive physical features, such as widely tunable nanogel size and drug loading capacity for Cy-R6G, intriguing fluorescence properties, high co-assembled structural stability in normal aqueous environments, enhanced anti-hemolytic characteristics, sensitive dual CO2/pH-responsive behavior, and precise and easily controllable CO2-induced release of Cy-R6G. Cytotoxicity assays clearly indicated that, due to the presence of cytosine receptors on the surface of cancer cells, Cy-R6G-loaded nanogels exert selective cytotoxicity against cancer cells in pristine culture medium, but do not affect the viability of normal cells. Surprisingly, in CO2-rich culture medium, Cy-R6G-loaded nanogels exhibit a further significant enhancement in cytotoxicity against cancer cells, and remain non-cytotoxic to normal cells. More importantly, a series of in vitro experiments demonstrated that compared to pristine culture medium, CO2-rich culture medium promotes more rapid selective internalization of Cy-R6G-loaded nanogels into cancer cells through cytosine-mediated macropinocytosis and thus accelerates the induction of apoptosis. Therefore, this newly developed system provides novel avenues for the development of highly effective CO2-responsive drug delivery systems with potent anticancer capabilities. |
| format | Article |
| id | doaj-art-d4cfa284f0a4486089f3cd25ae205d5a |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-d4cfa284f0a4486089f3cd25ae205d5a2024-12-14T06:32:16ZengElsevierMaterials Today Bio2590-00642024-12-0129101319Potential of a CO2-Responsive supramolecular drug-carrier system as a safer and more effective treatment for cancerEnyew Alemayehu Bayle0Fasih Bintang Ilhami1Jem-Kun Chen2Chih-Chia Cheng3Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, 10607, TaiwanGraduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, 10607, Taiwan; Department of Natural Science, Faculty of Mathematics and Natural Science, Universitas Negeri Surabaya, Surabaya, 60231, IndonesiaDepartment of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, 10607, TaiwanGraduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, 10607, Taiwan; Advanced Membrane Materials Research Center, National Taiwan University of Science and Technology, Taipei, 10607, Taiwan; Corresponding author. Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, 10607, Taiwan.We combined carbon dioxide (CO2)-responsive cytosine-containing rhodamine 6G (Cy-R6G) as a hydrophobic anticancer agent with hydrogen-bonded cytosine-functionalized polyethylene glycol (Cy-PEG) as a hydrophilic supramolecular carrier to construct a CO2-responsive drug delivery system, with the aim of enhancing the responsiveness of the system to the tumor microenvironment and thus the overall effectiveness of anticancer therapy. Due to self-complementary hydrogen bonding interactions between cytosine units, Cy-R6G and Cy-PEG co-assemble in water to form spherical-like nanogels, with Cy-R6G effectively encapsulated within the nanogels. The nanogels exhibit several distinctive physical features, such as widely tunable nanogel size and drug loading capacity for Cy-R6G, intriguing fluorescence properties, high co-assembled structural stability in normal aqueous environments, enhanced anti-hemolytic characteristics, sensitive dual CO2/pH-responsive behavior, and precise and easily controllable CO2-induced release of Cy-R6G. Cytotoxicity assays clearly indicated that, due to the presence of cytosine receptors on the surface of cancer cells, Cy-R6G-loaded nanogels exert selective cytotoxicity against cancer cells in pristine culture medium, but do not affect the viability of normal cells. Surprisingly, in CO2-rich culture medium, Cy-R6G-loaded nanogels exhibit a further significant enhancement in cytotoxicity against cancer cells, and remain non-cytotoxic to normal cells. More importantly, a series of in vitro experiments demonstrated that compared to pristine culture medium, CO2-rich culture medium promotes more rapid selective internalization of Cy-R6G-loaded nanogels into cancer cells through cytosine-mediated macropinocytosis and thus accelerates the induction of apoptosis. Therefore, this newly developed system provides novel avenues for the development of highly effective CO2-responsive drug delivery systems with potent anticancer capabilities.http://www.sciencedirect.com/science/article/pii/S2590006424003806CytosineCO2 responsivenessHypercapnic tumor microenvironmentSupramolecular drug-carrier systemSelective cellular uptake and cytotoxicity |
| spellingShingle | Enyew Alemayehu Bayle Fasih Bintang Ilhami Jem-Kun Chen Chih-Chia Cheng Potential of a CO2-Responsive supramolecular drug-carrier system as a safer and more effective treatment for cancer Materials Today Bio Cytosine CO2 responsiveness Hypercapnic tumor microenvironment Supramolecular drug-carrier system Selective cellular uptake and cytotoxicity |
| title | Potential of a CO2-Responsive supramolecular drug-carrier system as a safer and more effective treatment for cancer |
| title_full | Potential of a CO2-Responsive supramolecular drug-carrier system as a safer and more effective treatment for cancer |
| title_fullStr | Potential of a CO2-Responsive supramolecular drug-carrier system as a safer and more effective treatment for cancer |
| title_full_unstemmed | Potential of a CO2-Responsive supramolecular drug-carrier system as a safer and more effective treatment for cancer |
| title_short | Potential of a CO2-Responsive supramolecular drug-carrier system as a safer and more effective treatment for cancer |
| title_sort | potential of a co2 responsive supramolecular drug carrier system as a safer and more effective treatment for cancer |
| topic | Cytosine CO2 responsiveness Hypercapnic tumor microenvironment Supramolecular drug-carrier system Selective cellular uptake and cytotoxicity |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424003806 |
| work_keys_str_mv | AT enyewalemayehubayle potentialofaco2responsivesupramoleculardrugcarriersystemasasaferandmoreeffectivetreatmentforcancer AT fasihbintangilhami potentialofaco2responsivesupramoleculardrugcarriersystemasasaferandmoreeffectivetreatmentforcancer AT jemkunchen potentialofaco2responsivesupramoleculardrugcarriersystemasasaferandmoreeffectivetreatmentforcancer AT chihchiacheng potentialofaco2responsivesupramoleculardrugcarriersystemasasaferandmoreeffectivetreatmentforcancer |