Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals and Instrumentation
2.2. Synthesis of Complex 1
2.3. In Vitro Studies
2.3.1. Cell Viability
2.3.2. Estimation of ROS Formation
2.3.3. Cellular Internalization
2.3.4. DNA-Bound Pt
2.4. In Vivo Studies
2.4.1. Animal Studies
2.4.2. Tolerability Assessment
2.4.3. Orthotopic Intracranial GB Model by Stereotactic Injection of GL261 Cells
2.4.4. In Vivo MRI Assessment of Tumor Evolution
2.4.5. Antitumor Efficacy In Vivo
2.5. Statistical Analysis
3. Results and Discussion
3.1. Synthesis and Characterization
3.2. In Vitro Studies
3.2.1. Cytotoxicity and Cell Internalization
3.2.2. Pt Bound to DNA
3.2.3. Oxidative Stress Assay
3.3. In Vivo Studies
3.3.1. Tolerability Assessment in Mice
3.3.2. Efficacy Evaluation In Vivo
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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IC50 (μM) | ||||
---|---|---|---|---|
Time | Cell Lines | |||
Compounds | 1Br3G | HeLa | GL261 | |
24 h | complex 1 | 56.09 ± 1.18 | 29.94 ± 1.04 | 17.40 ± 1.08 |
CDDP | 45.07 ± 4.60 | 15.98 ± 1.04 | 5.61 ± 0.28 | |
DSCP | NT b | NT b | NT b | |
NDGA | NT b | 164.15 ± 0.02 | 109.45 ± 1.95 | |
72 h | complex 1 | 10.80 ± 0.60 | 1.85 ± 0.36 | 4.17 ± 0.12 |
CDDP | 4.63 ± 0.42 | 2.34 ± 0.30 | 2.16 ± 0.26 | |
DSCP | NT b | NT b | NT b | |
NDGA | 119.00 ± 14.20 | 55.65 ± 6.21 | 81.73 ± 2.40 |
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Mao, X.; Wu, S.; Calero-Pérez, P.; Candiota, A.P.; Alfonso, P.; Bruna, J.; Yuste, V.J.; Lorenzo, J.; Novio, F.; Ruiz-Molina, D. Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment. Cancers 2022, 14, 410. https://doi.org/10.3390/cancers14020410
Mao X, Wu S, Calero-Pérez P, Candiota AP, Alfonso P, Bruna J, Yuste VJ, Lorenzo J, Novio F, Ruiz-Molina D. Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment. Cancers. 2022; 14(2):410. https://doi.org/10.3390/cancers14020410
Chicago/Turabian StyleMao, Xiaoman, Shuang Wu, Pilar Calero-Pérez, Ana P. Candiota, Paula Alfonso, Jordi Bruna, Victor J. Yuste, Julia Lorenzo, Fernando Novio, and Daniel Ruiz-Molina. 2022. "Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment" Cancers 14, no. 2: 410. https://doi.org/10.3390/cancers14020410