Synergistic Antitumor Potency of a Self-Assembling Cyclodextrin Nanoplex for the Co-Delivery of 5-Fluorouracil and Interleukin-2 in the Treatment of Colorectal Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture Studies
2.1.1. Real-Time Cell Viability Analysis (RTCA)
2.1.2. Antitumoral Activity of CD Nanoplexes on 3D Spheroid Tumor Culture
2.1.3. Apoptosis Assays in 3D Spheroid Tumor Culture
2.1.4. Light Microscopy Analysis of 3D Tumor Cells in Plastic Blocks
2.1.5. Immunocytochemical Analysis of 3D Spheroid Tumor Culture
2.1.6. Assessment of Biological Activity of IL-2
2.2. In Vivo Studies
2.2.1. Safety Studies of CD Polymers
2.2.2. Assessment of In vivo Antitumor Activity of CD Nanoplexes
2.2.3. Histomorphometry on Cancer Nodules
2.3. Statistical Analysis
3. Results
3.1. Cell Culture Studies
3.1.1. Real-Time Proliferation Analysis
3.1.2. Antitumoral Activity of CD Nanoplexes on 3D Cultured Spheroid Tumor
3.1.3. Apoptosis Assays of 3D Tumor Model Using TUNEL
3.1.4. Light Microscopy Analysis of 3D Tumor Cells on Plastic Blocks
3.1.5. Immunocytochemical Examination in 3D Tumor Cells
3.1.6. Assessment of Biological Activity of IL-2
3.2. In Vivo Studies
3.2.1. Safety Studies of CD Polymers
3.2.2. Antitumor Activities of CD Nanoplexes
3.2.3. Histomorphometric Evaluation of In Vivo Cancer Nodules
4. Discussion
4.1. Cell Culture Studies
4.1.1. xCELLigence Real-Time Cell Analysis
4.1.2. Antitumoral Activity of CD Nanoplexes on 3D Spheroid Tumor Culture
4.1.3. Apoptosis Assays of 3D Tumor Model Using TUNEL
4.1.4. Light Microscopy Analysis of 3D Tumor Cells at Plastic Blocks
4.1.5. Immunocytochemical Examination in 3D Tumor Cells
4.1.6. Assessment of Biological Activity of IL-2
4.2. In Vivo Studies
4.2.1. Safety Studies of CD Polymers
4.2.2. Antitumor Activities of CD Nanoplexes
4.2.3. Histopathological Evaluation of In Vivo Cancer Nodules
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Abbreviation | Cyclodextrin Polymers | DS | MW | CLR | CD |
---|---|---|---|---|---|
CD1 | Quaternary-Ammonium-βCD polymer HCl, cross-linked with epichlorohydrin | 2.2 | 40,000 | 11 | 2.2 |
CD2 | Amino-βCD polymer HCl, cross-linked with epichlorohydrin | 1 | 25,000 | 10 | 1 |
CD3 | Guanidino-βCD polymer HCl, cross-linked with epichlorohydrin | 1 | 26,000 | 10 | 1 |
Treatment Groups | ||||
---|---|---|---|---|
PBS | CD1 | CD2 | CD3 | |
AST (55-352 U/L) | 367 ± 2.8 | 748 ± 8.5 | 316.5 ± 4.9 | 586 ± 4.2 |
ALT (41-131 U/L) | 71 ± 2.8 | 71 ± 1.4 | 53.5 ± 0.7 | 79 ± 2.8 |
cCRP (mg/dL) | <0.3 | <0.3 | <0.3 | <0.3 |
AST/ALT | 5.2 ± 0.1 | 10.5 ± 0.4 | 5.9 ± 0 | 7.4 ± 0.3 |
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Akkın, S.; Varan, G.; Işık, A.; Gökşen, S.; Karakoç, E.; Malanga, M.; Esendağlı, G.; Korkusuz, P.; Bilensoy, E. Synergistic Antitumor Potency of a Self-Assembling Cyclodextrin Nanoplex for the Co-Delivery of 5-Fluorouracil and Interleukin-2 in the Treatment of Colorectal Cancer. Pharmaceutics 2023, 15, 314. https://doi.org/10.3390/pharmaceutics15020314
Akkın S, Varan G, Işık A, Gökşen S, Karakoç E, Malanga M, Esendağlı G, Korkusuz P, Bilensoy E. Synergistic Antitumor Potency of a Self-Assembling Cyclodextrin Nanoplex for the Co-Delivery of 5-Fluorouracil and Interleukin-2 in the Treatment of Colorectal Cancer. Pharmaceutics. 2023; 15(2):314. https://doi.org/10.3390/pharmaceutics15020314
Chicago/Turabian StyleAkkın, Safiye, Gamze Varan, Anıl Işık, Sibel Gökşen, Elif Karakoç, Milo Malanga, Güneş Esendağlı, Petek Korkusuz, and Erem Bilensoy. 2023. "Synergistic Antitumor Potency of a Self-Assembling Cyclodextrin Nanoplex for the Co-Delivery of 5-Fluorouracil and Interleukin-2 in the Treatment of Colorectal Cancer" Pharmaceutics 15, no. 2: 314. https://doi.org/10.3390/pharmaceutics15020314
APA StyleAkkın, S., Varan, G., Işık, A., Gökşen, S., Karakoç, E., Malanga, M., Esendağlı, G., Korkusuz, P., & Bilensoy, E. (2023). Synergistic Antitumor Potency of a Self-Assembling Cyclodextrin Nanoplex for the Co-Delivery of 5-Fluorouracil and Interleukin-2 in the Treatment of Colorectal Cancer. Pharmaceutics, 15(2), 314. https://doi.org/10.3390/pharmaceutics15020314