Biomaterials Science Blog

Researchers have demonstrated that controlling nanoparticle shape and packing can impact how cancer therapeutics interact with cells.

Photodynamic therapy is an innovative emerging therapy for cancer.  This therapeutic modality consists of introducing light-activated molecules known as ‘photosensitizers’ into cancer cells.  When activated with light, these photosensitizers are able to produce toxic molecules within the cells (also known as reactive oxygen species or ROS) that can eventually cause cancer cell death.  Photosensitizers are often introduced into the cells using nanoparticle carriers. In order for effective cell death to occur, ROS must be formed within the nanoparticles and then diffuse out of the nanoparticles into the cells.

In this article, Chu et al. have designed silica-based nanocarriers that can control how photosensitizers interact with cells. They previously found that when photosensitizer-loaded nanoparticles were packed more densely, the amount of ROS that was released decreased.  In contrast, more loosely packed nanoparticles allowed for greater release of ROS into cells. In this study, the researchers designed a third type of nanoparticle consisting of a gold nanorod coated with dense silica. They found that this third type of nanoparticle released photosensitizers much more efficiently than the either densely packed or loosely packed silica-only particles. They also discovered that the nanorod-based particles produced a different distribution of ROS as compared to the loose or dense silica-only particles. When cells were treated with these nanoparticles, loosely-packed silica particles and the nanorod-based particles demonstrated dramatic decreases in cell-viability due to the action of the photosensitizers. Further, while the silica-based loose and dense particles caused cells to die via a programmed cell death (apoptotic) route, the nanorod-based particles caused cell death via cell injury resulting in premature cell death (necrosis).

These experiments suggest that controlling the composition and shape of the nanoparticles that carry photosensitizers to cancer cells can alter both the number of cancer cells killed as well as the mechanism by which the cells die. This work has implications for future photodynamic therapeutic strategies.

Debanti Sengupta recently completed her PhD in Chemistry from Stanford University.  She is currently a Siebel postdoctoral scholar at the University of California, Berkeley.

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This paper by Sunami et al. studies the impact of 3D patterning on cells, and shows that cells grown on 3D micropatterns respond by changing their migration speed, their proliferation rate, and their expression of actin.

It is standard laboratory practice to grow cells outside the body on flat tissue culture plates.  However, cells inside the body are surrounded by other cells and connective tissue organized in three dimensions.  It is therefore very important to develop culture platforms for cells that more accurately capture a cell’s microenvironment inside the body. 

In this paper, the authors developed a three-dimensional culture platform that could be modified to study the properties of fibroblasts (skin cells) in culture. The authors changed only one factor – the area of the three-dimensional triangles that the cells were cultured on – to study the impact of 3D micropatterned areas on fibroblasts. The resultant surfaces that they used were about as adhesive as a smooth glass surface.  Interestingly, they found that fibroblast spreading was very different on surfaces with different areas, with maximum cell spreading observed on a surface with an intermediate pattern area.  The cells primarily adhered to the upper surface of the 3D micropatterns. Further, the density of the cells was also dependent on the micropattern area – as micropattern area increased, the density of the cells correspondingly increased as well. The cells also proliferated faster on surfaces with larger micropattern areas, while cell proliferation slowed on smaller triangles. The authors then used timelapse microscopy to study how these cells migrated over time, and found that while cells migrated more slowly on all of the micropatterned surfaces as compared to a completely flat surface, migration was slowest on the micropatterns with the smallest areas. Similarly, the authors found that f-actin expression was increased on the patterns with the largest areas. The authors hypothesize that this may mean that cells experience less mechanical stress as pattern size decreases.

Influence of the pattern size of micropatterned scaffolds on cell morphology, proliferation, migration and F-actin expression
Hiroshi Sunami, Ikuko Yokota and Yasuyuki Igarashi
Biomater. Sci., 2014, Advance Article DOI: 10.1039/C3BM60237K

Debanti Sengupta recently completed her PhD in Chemistry from Stanford University.  She is currently a Siebel postdoctoral scholar at the University of California, Berkeley.  

Follow the latest journal news on Twitter @BioMaterSci or go to our Facebook page.

Cancer is the second leading cause of death worldwide, and continues to be a challenging disease to treat therapeutically. One strategy to treat cancer patients is to surgically remove the primary tumor and attempt to prevent the spread of cancer cells to other organs in the body. Unfortunately, surgical resection of tumors may be difficult in sensitive organs (e.g. the brain), and tumors may need to be treated directly with chemotherapy drugs to inhibit growth.

Recently, there has been an increased interest in utilizing biomaterials to deliver chemotherapy drugs directly to the primary tumor. Current research at the Indian Institute of Technology explores the use of nanohydrogels supplemented with iron oxide magnetic nanoparticles as a vehicle to deliver chemotherapy drugs to the primary tumor. Interestingly, these thermo-responsive nanohydrogels could release their anticancer drug cargo when heated with a magnetic field. Although this study did not use chemotherapy drugs, the magnetic hydrogels were used to heat the tumor locally to reduce tumor size – upon stimulation with a magnetic field. This study focused on characterizing the material properties of the magnetic nanohydrogels, in addition to analyzing the effects of the nanohydrogel on inhibiting tumor growth.

The magnetic nanohydrogel is composed of iron oxide nanoparticles, chitosan, and poly-N-isopropylacrylamide (NIPAAm).  The chitosan-poly-(NIPAAm) nanohydrogels are hydrophilic below the lower critical solution temperature (LCST) of 42^oC. When stimulated with the appropriate magnetic field, the magnetic nanoparticles heat the hydrogel above the LCST. When the temperature is increased above the LCST, the polymers in the hydrogel change from “expanded coils” to “compact globules,” and cause the release of the aqueous contents of the hydrogel. The hydrophilic to hydrophobic transition is the main mechanism by which the anticancer drug cargo could be released from the hydrogel.

The biocompatibility and efficacy of the hydrogel in reducing tumor growth in vivo were analyzed. Using a mouse model of fibrosarcoma, the magnetic nanohydrogels were delivered via injection to the primary tumor site, and then stimulated with a magnetic field. Various biocompatibility studies were conducted, showing that serum protein concentrations and blood cell counts were not affected. The biodistribution of the magnetic hydrogel was also quantified, with minimal accumulation of the nanohydrogel in various organs (14 days post-delivery). Additionally, the magnetic nanohydrogel decelerated the growth of the primary tumor. After magnetic stimulation, the magnetic particles in the nanohydrogel successfully heated the tumor locally with minimal damage to the surrounding tissues. Despite not containing chemotherapy drugs, the magnetic nanohydrogels were still efficient in inhibiting the primary tumor growth.

This study describes the thermo-responsive properties of magnetic nanohydrogels, and demonstrates the ability to reduce tumor size using nanohydrogels heated with a magnetic field. Future studies are needed to show efficacy in delivering chemotherapy drugs using the magnetic nanohydrogels as a delivery vehicle. Still, the magnetic nanohydrogels are a promising platform for a minimally invasive method of decreasing tumor growth in vivo.

Biocompatibility, biodistribution and efficacy of magnetic nanohydrogels in inhibiting growth of tumors in experimental mice models
Manish K. Jaiswal, Manashjit Gogoi, Haladhar Dev Sarma, Rinti Banerjee and D. Bahadur
Biomater. Sci., 2014, Advance Article DOI: 10.1039/C3BM60225G

Brian Aguado is currently a Ph.D. Candidate and NSF Fellow in the Biomedical Engineering department at Northwestern University. He holds a B.S. degree in Biomechanical Engineering from Stanford University and a M.S. degree in Biomedical Engineering from Northwestern University. When he’s not in the lab, Brian enjoys traveling, cooking, swimming, and spending time with family and friends. Read more about Brian’s research publications here.

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