Computational Analysis of Nanocarriers in the Tumor Microenvironment for the Treatment of Colorectal Cancer
Abstract
:1. Introduction
2. Results
2.1. Results on Selected Samples
2.1.1. First Sample
2.1.2. Second Sample
2.1.3. Third Sample
2.2. Validation of 2D Sample Results
3. Discussion
- The interstitial space between at least one pair of glands is narrow, which increases the velocity of the interstitial fluid, driving the liposomes through the streamlines at speeds sufficient to escape the electrostatic surface attraction forces of the cancerous glands;
- The interstitial space between at least one pair of glands is narrow enough so that the liposomes transiting in between, despite increasing their speed, have a trajectory close enough to the boundary layer of the gland surface, which slows down their speed and allows attractive forces to act on the liposome, increasing the probability of engagement with the cancerous region;
- A pair of glands is sufficiently separated so that the interstitial fluid does not show significant increases in velocity, which can cause liposomes to transit in regions distant from the cancerous glands, making it difficult for the two bodies to attract, and as a result, decreasing the effectiveness of the coupling;
- Even though a pair of glands is sufficiently separated, changes in velocities and trajectories produced by morphological conditions in more superficial layers can give rise to the transit of liposomes in regions with low velocities that are close to the surface of the gland. Malignant glands benefit from the attraction and subsequent coupling between positively charged liposomes and negatively charged cancerous regions, especially when the glands are found in deeper regions of the tumor and with a more acidic pH, thus increasing the negative charge.
4. Materials and Methods
- Mobility of the fluid: allows for the identification of the behavior of the fluid through the sample and its corresponding velocities;
- Maximum depth reached by the particles: used to predict the time required to achieve a complete diffusion of liposomes in a determined tumor;
- Time: The time variable is essential to estimate how long it takes for the dose that achieves contact with the surface of the cancerous tissue to break through to the maximum depth of the sample. It is also especially important to determine the time required to register the first and last coupling between a liposome and a cancerous region.
4.1. Selection and Processing of the Samples to Be Studied
- Level of glandular deformation: the identification of the regions of malignancy using the geometric shape of the cellular glands, through the characteristics of glandular aberration; glands with more asymmetric characteristics and a higher Best Alignment Metric (BAM) value tended to be classified as malignant [44];
- Stage of the disease in TNM: T (local extension of the primary tumor at the time of diagnosis); N (regional lymph node status); and M (distant metastatic disease, including non-regional lymph nodes). The selected samples must belong to a stage of the disease between stages II and III;
- Presence of benign and malignant glands in the same sample: to demonstrate the selective behavior of the nanoparticles, the histological sample must have both benign and natural cell groups, as well as malignant cell regions.
4.2. Calculation of Interstitial Fluid Mass Flow
4.3. Calculation of the Mass Flow of Liposomes
4.4. Models for Interstitial Fluid
4.5. Model for the Movement of Particles
- : drag forces acting on the particle;
- : buoyancy forces;
- : forces due to rotation;
- : Force associated with the pressure gradient. This is the force applied to the particle due to the pressure gradient in the fluid surrounding the particle caused by the acceleration of the fluid. This is only significant when the density of the fluid is comparable to or greater than the density of the particle;
- : force associated with the electrostatic interaction of the particle immersed in the electric field produced by the negative charge on the surface of the malignant cell.
- = fluid viscosity;
- = particle density;
- = particle diameter;
- Re = Reynolds number;
- = particle velocity;
- = fluid velocity;
- = drag coefficient;
- = particle mass flow;
- = timestep or step of time.
- = additional forces of interaction, such as the electrostatic force that induces selective coupling [51].
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Description | Units | Symbol |
---|---|---|
Fluid mobility | m/s | |
Vectorized deposition efficiency | % | |
Maximum depth reached by the particles | m | d |
Time | s | t |
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Morales, E.V.; Guerrero, G.S.; Hoyos Palacio, L.M.; Maday, Y. Computational Analysis of Nanocarriers in the Tumor Microenvironment for the Treatment of Colorectal Cancer. Appl. Sci. 2023, 13, 6248. https://doi.org/10.3390/app13106248
Morales EV, Guerrero GS, Hoyos Palacio LM, Maday Y. Computational Analysis of Nanocarriers in the Tumor Microenvironment for the Treatment of Colorectal Cancer. Applied Sciences. 2023; 13(10):6248. https://doi.org/10.3390/app13106248
Chicago/Turabian StyleMorales, Esteban Vallejo, Gustavo Suárez Guerrero, Lina M. Hoyos Palacio, and Yvon Maday. 2023. "Computational Analysis of Nanocarriers in the Tumor Microenvironment for the Treatment of Colorectal Cancer" Applied Sciences 13, no. 10: 6248. https://doi.org/10.3390/app13106248
APA StyleMorales, E. V., Guerrero, G. S., Hoyos Palacio, L. M., & Maday, Y. (2023). Computational Analysis of Nanocarriers in the Tumor Microenvironment for the Treatment of Colorectal Cancer. Applied Sciences, 13(10), 6248. https://doi.org/10.3390/app13106248