Motivation Current Leading Approach Our Approach Analytical and
Graduate Category: Engineering and Technology Degree Level: PhD. Abstract ID# 860
Towards accumulation of magnetic nanoparticles into tissues of small porosity Rasam Soheilian and Randall M. Erb
Motivation
Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA USA
Cancer is one of the most acute health issues in our society nowadays and almost 30% of all deaths each year are due to cancer [1]. In the past decades, chemotherapy has been the only way to treat cancer but there are issues related to this method such as side effects and not being able to destroy all cancer (neoplastic) cells [2]. It is depicted that drug-laden magnetic nanoparticles can improve the efficiency of the drug delivery [3]. These particles can be guided through human’s body by using a magnetic source which has a strong field and also a high field gradient.
Our Approach
Current Leading Approach Before Targeting
Tumor site
After Targeting
Tumor site MNP concentrated
MRI images of a mouse brain taken prior to β-GLU-MNP administration and at 60 min post-administration with magnetic targeting (Courtesy of A.E. David, taken from 3).
However, Using such a source will cause the nanoparticles to form chains and aggregations that are larger than the size of the tumor pores. It is believed that the aggregate sizes are too large to effectively permeate the pores in the tumor cell network. This effect is going to lower the efficiency of drug delivery. In this work, we demonstrate that by using advanced field functions for our magnetic fields we can manipulate the field and gradient to break up this magnetic nanoparticles.
Zhou et al. [3] demonstrated that magnetic nanoparticles could be used for drug delivery to brain tumors in a mouse model through magnetic targeting. Despite the local enhancement of drug concentration, the efficiency of drug delivery is still low likely due to aggregation of the MNPs preventing them from entering into the tumor cellular tissue.
Aggregated MNPs won’t penetrate tumor tissue
Modeling Results
In a linear magnetic field MNPs will simply chain parallel to the external field due to dipolar interaction. Instead, with advanced field functions, dynamic magnetic fields continuously change the energy landscape forcing the MNPs to be constantly out of equilibrium. These dynamics are dictated by viscous drags that need to be taken into account. To better understand these systems we first characterize a symmetric rotating magnetic field.
Matlab Simulation
To verify our analytic expression, a numerical simulation has been developed to observe separation events between particles at different frequencies. Separation vs. time for a micro-particle with χ=0.163 and η=2.5 mPa s. Critical frequency solved analytically and numerically for different viscosities.
Stokes Force
Brownian Force
−6𝜋𝜋𝑎𝑎
𝜋𝑘𝐵 𝑇 2 𝑁(𝑡) = 𝜉 ∆𝑡𝑡
Critical frequency is the frequency that gives the highest separation possible between particles. This non-linear response shows the importance of tailoring the field characteristics to the specific system
𝑭𝒏𝒏𝒏 = 𝑭𝒔𝒔𝒔𝒔𝒔𝒔 + 𝑭𝒎𝒎𝒎𝒎𝒎𝒎𝒎𝒎 + 𝑵(𝒕) Phase-Slip Regime
Phase-Locked Regime MNPs remained aggregated
With Advanced Field Functions
Instead of simple linear magnetic fields that lead to aggregation, we employ advanced field functions that allow the MNPs to be concentrated locally while utilizing inter-particle force dynamics to continuously drive separation events, thus preventing aggregation.
Analytical and Numerical Model
Magnetic Dipolar Force 3𝑚2 4𝜋𝜇0 𝑟 4
With Linear Magnetic Field
MNPs have separation events
Critical Frequency
When the phase lag reaches 45𝑜 , the magnetic force is at its maximum value. Any additional viscous force would lead to phase slip – a separation event.
Advanced field functions can further enhance separation events that allow de-aggregation
Experimental and Numerical Results
Measuring the separation events of a pair of magnetic particles
Images of 150 nm particles were obtained using a custom dark-field microscope setup. In all, H = 100 Oe.
(a) Schematics of the in-vitro setup. (b) Percentage of the delivered MNPs after applying dynamic and static magnetic field for one hour.
10 µm
10 µm
Experiments have been done to obtain the critical frequency for different size particles in different viscosities. At lower frequencies, particles were still able to form linear aggregates. For frequencies larger than fc, the linear aggregates were destroyed.
Conclusions
Here we suggest a method for using drug laden magnetic nanoparticles under applied rotating magnetic fields. This technique is going to resolve the issue of particles aggregating during magnetic targeting that has been previously observed. By implementing advanced field functions like rotating magnetic fields a dynamic energy
(a-c) 150 nm magnetic particles were concentrated at a target region with an easily achievable magnetic field gradient of 60 Oe/cm. The applied magnetic field was 165 Oe. (b) Under field rotation (while maintaining 165 Oe and 60 Oe/cm), the magnetic nanoparticles quickly de-aggregate. (c) Immediately after stopping field rotation, the linear aggregation of the nanoparticles resumes.
landscape causes the particle aggregates to break up so that they may enter the smallest capillaries such as tumor pores. In- vitro experiments show that penetration of the MNPs is enhanced by 2-fold with dynamic magnetic fields compared to static fields. This result suggests that dynamic fields could indeed provide a large enhancement to the efficiency of magnetic targeting.
Contact Information: Rasam Soheilian, [email protected] or Prof. Randall M. Erb, [email protected] 334 Snell Engineering Center, 360 Huntington Avenue, Boston, MA 02115, USA
References: [1] Jemal A., Siegel R., Xu J. and Ward E., Cancer J. Clin., 2010, 60, 277. [2] Rooseboom M, Commandeur J.N. and Vermeulen N.P., Pharmacol. Rev., 2004, 56, 53. [3] Zhou J., Zhang J., David A.E., Yang V.C., Nanotechnology, 2013, 24, 375102.
Towards accumulation of magnetic nanoparticles into tissues of small porosity Rasam Soheilian and Randall M. Erb
Motivation
Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA USA
Cancer is one of the most acute health issues in our society nowadays and almost 30% of all deaths each year are due to cancer [1]. In the past decades, chemotherapy has been the only way to treat cancer but there are issues related to this method such as side effects and not being able to destroy all cancer (neoplastic) cells [2]. It is depicted that drug-laden magnetic nanoparticles can improve the efficiency of the drug delivery [3]. These particles can be guided through human’s body by using a magnetic source which has a strong field and also a high field gradient.
Our Approach
Current Leading Approach Before Targeting
Tumor site
After Targeting
Tumor site MNP concentrated
MRI images of a mouse brain taken prior to β-GLU-MNP administration and at 60 min post-administration with magnetic targeting (Courtesy of A.E. David, taken from 3).
However, Using such a source will cause the nanoparticles to form chains and aggregations that are larger than the size of the tumor pores. It is believed that the aggregate sizes are too large to effectively permeate the pores in the tumor cell network. This effect is going to lower the efficiency of drug delivery. In this work, we demonstrate that by using advanced field functions for our magnetic fields we can manipulate the field and gradient to break up this magnetic nanoparticles.
Zhou et al. [3] demonstrated that magnetic nanoparticles could be used for drug delivery to brain tumors in a mouse model through magnetic targeting. Despite the local enhancement of drug concentration, the efficiency of drug delivery is still low likely due to aggregation of the MNPs preventing them from entering into the tumor cellular tissue.
Aggregated MNPs won’t penetrate tumor tissue
Modeling Results
In a linear magnetic field MNPs will simply chain parallel to the external field due to dipolar interaction. Instead, with advanced field functions, dynamic magnetic fields continuously change the energy landscape forcing the MNPs to be constantly out of equilibrium. These dynamics are dictated by viscous drags that need to be taken into account. To better understand these systems we first characterize a symmetric rotating magnetic field.
Matlab Simulation
To verify our analytic expression, a numerical simulation has been developed to observe separation events between particles at different frequencies. Separation vs. time for a micro-particle with χ=0.163 and η=2.5 mPa s. Critical frequency solved analytically and numerically for different viscosities.
Stokes Force
Brownian Force
−6𝜋𝜋𝑎𝑎
𝜋𝑘𝐵 𝑇 2 𝑁(𝑡) = 𝜉 ∆𝑡𝑡
Critical frequency is the frequency that gives the highest separation possible between particles. This non-linear response shows the importance of tailoring the field characteristics to the specific system
𝑭𝒏𝒏𝒏 = 𝑭𝒔𝒔𝒔𝒔𝒔𝒔 + 𝑭𝒎𝒎𝒎𝒎𝒎𝒎𝒎𝒎 + 𝑵(𝒕) Phase-Slip Regime
Phase-Locked Regime MNPs remained aggregated
With Advanced Field Functions
Instead of simple linear magnetic fields that lead to aggregation, we employ advanced field functions that allow the MNPs to be concentrated locally while utilizing inter-particle force dynamics to continuously drive separation events, thus preventing aggregation.
Analytical and Numerical Model
Magnetic Dipolar Force 3𝑚2 4𝜋𝜇0 𝑟 4
With Linear Magnetic Field
MNPs have separation events
Critical Frequency
When the phase lag reaches 45𝑜 , the magnetic force is at its maximum value. Any additional viscous force would lead to phase slip – a separation event.
Advanced field functions can further enhance separation events that allow de-aggregation
Experimental and Numerical Results
Measuring the separation events of a pair of magnetic particles
Images of 150 nm particles were obtained using a custom dark-field microscope setup. In all, H = 100 Oe.
(a) Schematics of the in-vitro setup. (b) Percentage of the delivered MNPs after applying dynamic and static magnetic field for one hour.
10 µm
10 µm
Experiments have been done to obtain the critical frequency for different size particles in different viscosities. At lower frequencies, particles were still able to form linear aggregates. For frequencies larger than fc, the linear aggregates were destroyed.
Conclusions
Here we suggest a method for using drug laden magnetic nanoparticles under applied rotating magnetic fields. This technique is going to resolve the issue of particles aggregating during magnetic targeting that has been previously observed. By implementing advanced field functions like rotating magnetic fields a dynamic energy
(a-c) 150 nm magnetic particles were concentrated at a target region with an easily achievable magnetic field gradient of 60 Oe/cm. The applied magnetic field was 165 Oe. (b) Under field rotation (while maintaining 165 Oe and 60 Oe/cm), the magnetic nanoparticles quickly de-aggregate. (c) Immediately after stopping field rotation, the linear aggregation of the nanoparticles resumes.
landscape causes the particle aggregates to break up so that they may enter the smallest capillaries such as tumor pores. In- vitro experiments show that penetration of the MNPs is enhanced by 2-fold with dynamic magnetic fields compared to static fields. This result suggests that dynamic fields could indeed provide a large enhancement to the efficiency of magnetic targeting.
Contact Information: Rasam Soheilian, [email protected] or Prof. Randall M. Erb, [email protected] 334 Snell Engineering Center, 360 Huntington Avenue, Boston, MA 02115, USA
References: [1] Jemal A., Siegel R., Xu J. and Ward E., Cancer J. Clin., 2010, 60, 277. [2] Rooseboom M, Commandeur J.N. and Vermeulen N.P., Pharmacol. Rev., 2004, 56, 53. [3] Zhou J., Zhang J., David A.E., Yang V.C., Nanotechnology, 2013, 24, 375102.
