Modulation of the Microtubule Network for Optimization of Nanoparticle Dynamics for the Advancement of Cancer Nanomedicine
Abstract
:1. Introduction
- (a)
- Does NP size matter?
- (b)
- Will DTX concentration affect NP uptake, transport, and retention?
- (c)
- Does the relative timing of DTX and NP inoculation matter?
2. Materials and Methods
2.1. Cell Culture
2.2. GNP Preparation and Modification
2.3. Nanoparticle Surface Modification
2.4. Docetaxel (DTX) and GNP Inoculation
2.5. Cytotoxicity Assay
2.6. GNP Uptake and Retention Dynamics
2.7. Quantification of Uptake in Cells
2.8. Confocal Imaging
2.9. Measuring DNA Damage
2.10. Measuring Cell Survival Fraction
3. Results and Discussion
3.1. Effect of NP Size and Docetaxel Concentration on Intracellular Uptake of NPs
- (a)
- Following treatment with DTX, mitosis is arrested during metaphase. The prolonged time in M phase enables greater accumulation of NPs within cells. This led to the increase in uptake of NPs of both sizes.
- (b)
- The presence of DTX did not significantly affect the endocytosis process since it is a process largely governed by the actin cytoskeleton closer to the cell periphery [39]. The cells’ ability to maintain efficient endocytosis enabled significantly higher accumulation of smaller NPs in DTX-treated cells (seen in Figure 2c).
3.2. Distribution of Nanoparticles During Cell Division (Mitosis)
3.3. The Effect of the Docetaxel Concentration on the Intracellular Retention of NPs
3.4. Effect of GNPs on the Action of the Drug Docetaxel
3.5. The Relative Timing of DTX and GNP Inoculation
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Bannister, A.; Dissanayake, D.; Kowalewski, A.; Cicon, L.; Bromma, K.; Chithrani, D.B. Modulation of the Microtubule Network for Optimization of Nanoparticle Dynamics for the Advancement of Cancer Nanomedicine. Bioengineering 2020, 7, 56. https://doi.org/10.3390/bioengineering7020056
Bannister A, Dissanayake D, Kowalewski A, Cicon L, Bromma K, Chithrani DB. Modulation of the Microtubule Network for Optimization of Nanoparticle Dynamics for the Advancement of Cancer Nanomedicine. Bioengineering. 2020; 7(2):56. https://doi.org/10.3390/bioengineering7020056
Chicago/Turabian StyleBannister, Aaron, Dushanthi Dissanayake, Antonia Kowalewski, Leah Cicon, Kyle Bromma, and Devika B. Chithrani. 2020. "Modulation of the Microtubule Network for Optimization of Nanoparticle Dynamics for the Advancement of Cancer Nanomedicine" Bioengineering 7, no. 2: 56. https://doi.org/10.3390/bioengineering7020056