Bowdoin Science Journal

Sebastian Ortiz Gonzalez

LiNx: A Dual-Pronged Approach to Cancer Immunotherapy

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mRNA vaccines have emerged from the COVID-19 pandemic as a promising approach to fighting infectious diseases (Kutikuppala et al. 2024). Different from traditional vaccines, which use a weakened version of a virus, mRNA vaccines deliver an mRNA corresponding to a protein on the surface of the virus. This mRNA allows our immune system to recognize and make small parts of the virus so that it can create antibodies to combat it (Cleveland Clinic 2024). However, mRNA is an unstable and negatively charged molecule, so it must be encased with some type of transport protection to prevent its degradation during delivery (Kutikuppala et al. 2024).

Lipid nanoparticles, or LNPs, have gained popularity in recent years as an effective delivery platform for mRNA vaccines due to their highly tunable composition and their ability to prevent nucleic acid degradation (Xu et al., 2025). One popular example is the utilization of LNPs in the Moderna mRNA-1273 COVID vaccine, where mRNA encoding the protein on the outside of the virus that is recognized by the immune system was encapsulated in an LNP. Vaccination with this LNP-encapsulated mRNA resulted in 90% lower risk of contracting COVID within 21 days for those over the age of 16, demonstrating the power and possibility of this technology (Noor, 2021).

LNPs are extremely small particles composed of: 1) ionizable lipids, which act as a case for the nucleic acid being delivered; 2) phospholipids regulating cell membrane fusion; 3) PEG-lipids and 4) cholesterol which both affect its size and stability (Figure 1) (Xu et al., 2025). An LNP’s formulation can have substantial effects on its ability to avoid cellular barriers for vaccine mRNA entry to a targeted area. For example, degradation of LNPs by enzymes and/or other immune cells after entering the body can affect a vaccine’s ability to reach the targeted tissue (Hou et al., 2021). This is especially critical for scientists working on immunotherapies, as a variation in lipid composition can determine whether the LNP will be taken up by immune cells like dendritic cells or other antigen-presenting cells, which present the LNP to other immune cells and start the immune response (Hou et al., 2021). 

 

Figure showing the composition of LNPs. Phospholipid bilayer with cholesterol surrounds the LNP, which contains nucleic acid encapsulated within ionizable lipids
Figure 1. Composition of lipid nanoparticles. Adapted from 2025 Xu et al.

Hydrogels have also been utilized by scientists as vaccine carriers that can also augment immune responses. Hydrogels are natural or synthetic materials containing a 3D network of cross-linked polymer chains that allow them to absorb large amounts of a target substance (Ho et al. 2022). Depending on the composition of the hydrogel, scientists have found evidence of greatly increased immune cell recruitment and prolonged immune memory in mouse models of melanoma after a hydrogel-based vaccine was delivered (Kerr et al., 2023; Pal et al., 2024). In other words, the immune response was stronger and also more effective upon encountering a pathogen a second time. Therefore, if a hydrogel were to be used to deliver an LNP, finding the right composition is extremely important, as it can greatly impact its efficacy.

In their paper, Zhu et al. report the effectiveness of LiNx, a nanofiber-hydrogel composite (NHC) mRNA LNP matrix, in tumor and melanoma mouse models. Essentially, they embedded their LNPs within the 3D network of extremely small and cross-linked fibers in a hydrogel to significantly boost the immune response to cancer. 

LiNx works as a subcutaneous injection combining the potent immune activation capability of LNPs with the immunostimulatory microenvironment provided by the NHC. While the NHC recruits immune cells to the injection site and promotes immune cell signaling, the LNPs introduce nearby cells to the encapsulated mRNA, resulting in a coordinated adaptive immune response (Figure 2).

Diagram showing LiNx mechanism. It's delivered into the body, transfects non-APCs, enters an APC and is processed and presented through MHC1 or MHC2 pathways
Figure 2. Diagram of LiNx mechanism. (1) LiNx is delivered into the body and (2) transfects non-antigen-presenting cells. (3) The LNP enters an antigen-presenting cell, and the mRNA within is processed and presented through (4) two different pathways. Adapted from 2025 Zhu et al.

The lipid composition of LNPs can affect not only their size and stability, but also their transfection and delivery efficacy, or their ability to deliver the vaccine mRNA into host cells like dendritic cells (which start the immune response). To identify the top-performing LNP formulations, the researchers screened over one thousand different lipid compositions. Three top-performing LNP formulations were identified based on their transfection efficiency in bone marrow-derived dendritic cells: C10, D6, and F5. All of these formulations also separately activated powerful Th1 responses, a type of immune response meant to eliminate bacteria, viruses, and cancer cells, after three doses of subcutaneous injections.  

To simply quantify the host cell recruitment and transfection profile of the three different formulations, the researchers injected LiNx containing C10, D6, or F5 LNP into mice and measured the present immune cells 3 and 7 days post-injection. At both 3 and 7 days post-injection, a considerable amount of host cells were found in the NHC scaffold for all three formulations. The D6 formulation showed the greatest host cell recruitment, having a 12.6-fold increase compared to the control.

The researchers then performed a similar experiment, injecting mice with LiNx loaded with a test mRNA to get a better idea of the performance of each formulation compared to each other. They found that 10 days after injection, the D6 formulation contained over one-hundred-fold more transfected cells than C10 and F5-mRNA LiNx. Fourteen days post-injection, the D6-mRNA LiNx was also found to have recruited a more diverse range of immune cells associated with robust and specific immune responses like T cells and B cells. On the other hand, the C10 and F5-mRNA LiNx recruited more immune cells associated with general immune responses, like neutrophils. This shows that the D6-mRNA LiNx induces a stronger and more customized immune response. Additionally, three months post-vaccination, there were 10x more central memory T cells present in the spleens of D6-mRNA mice compared to the control and other formulations, indicating a stronger long-term memory response. These results suggest that the D6 LiNx is the most efficient LiNx formulation. 

Having characterized the immune activation induced by D6-mRNA LiNx, the researchers then tested its effectiveness in cancer mouse models. Mice were inoculated with colorectal cancer cells and received vaccinations of one of the LiNx formulations four days later. These mice were administered the vaccines in a single dose, while a separate control group received three doses of only D6 LNPs. The negative control group received only the NHC and protein without the LNP. The median survival time of the single-dose D6 LiNx mice was 75 days compared to 31 days for the negative control group and 37.5 days for the three-dose group, underscoring a heightened tumor suppression response. Fifty percent of these mice remained tumor-free after 100 days. This experiment demonstrated LiNx’s anti-cancer potential in vivo. 

In their paper, Zhu et al. demonstrated the effectiveness of a dual-modal approach to cancer immunotherapy. Through the combination of lipid nanoparticle mRNA delivery and a hydrogel microenvironment, they were able to induce a substantially stronger immune response characterized by tumor suppression and long-term immune memory in mouse models. The superior performance of a singular dose of D6 LiNx compared to three LNP doses illustrates the promise found in combining delivery methods with immune-boosting materials for the future development of stronger and longer-lasting cancer immunotherapies.

 

References:

Ho T-C et al. 2022. Hydrogels: Properties and Applications in Biomedicine. Molecules. 27(9):2902. 

Hou X, Zaks T, Langer R, Dong Y. 2021. Lipid nanoparticles for mRNA delivery. Nat Rev Mater. 6(12):1078–1094. 

Kerr MD et al. 2023. Biodegradable scaffolds for enhancing vaccine delivery. Bioeng Transl Med. 8(6):e10591. 

Kutikuppala LVS et al. 2024. Prospects and Challenges in Developing mRNA Vaccines for Infectious Diseases and Oncogenic Viruses. Med Sci (Basel). 12(2):28. 

mRNA Vaccines: What They Are & How They Work. 2024. Cleveland Clinic; [accessed 2026 May 2]. https://my.clevelandclinic.org/health/treatments/21898-mrna-vaccines

Noor R. 2021. Developmental Status of the Potential Vaccines for the Mitigation of the COVID-19 Pandemic and a Focus on the Effectiveness of the Pfizer-BioNTech and Moderna mRNA Vaccines. Curr Clin Microbiol Rep. 8(3):178–185. 

Pal S et al. 2024. Extracellular Matrix Scaffold-Assisted Tumor Vaccines Induce Tumor Regression and Long-Term Immune Memory. Adv Mater. 36(15):e2309843. 

Xu S et al. 2025. Lipid nanoparticles: Composition, formulation, and application. Mol Ther Methods Clin Dev. 33(2):101463. 

Zhu Y et al. 2025. An mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite for cancer immunotherapy. Nat Commun. 16(1):5707. 






MMOF Hydrogels: A New Tool in Aquatic Dye Removal

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Every year, over 280,000 tons of synthetic dyes are introduced into aquatic environments as wastage from textile mills. This significant amount of runoff accounts for the augmentation of environmental contamination in several countries, including China, and can have detrimental effects on aquatic life. For example, decreased red blood cell count has been observed in mosquitofish, and liver degeneration in Mozambique tilapia (Dutta et al. 2024).

Previous studies have attempted to use polyacrylamide hydrogels to selectively remove contaminants from an environment. However, the process of creating these hydrogels was found to be too complex and therefore impractical for real-world applications (He et al. 2021). Cheng et al. describe a sodium alginate hydrogel with increased selectivity to a pollutant, malachite green (MG) dye, and heightened adsorptive properties through enhancement with magnetic and MOF materials. 

Metal-organic frameworks, or MOFs, are a class of crystalline materials that are made up of a metal ion or cluster and organic linkers. They are extremely porous (~90% free volume) and have extremely high internal surface areas (beyond 6000m^2/g) (Zhou, Long, Yaghi. 2012). These properties, along with the adjustability of their composition, have made MOFs of interest for applications as high-capacity adsorbents for pollutants.

To create their MOF, the researchers dissolved two metal solids, FeCl3·6H2O & FeCl2·4H2O, in water and ethanol, centrifuged, and collected Fe3O4 nanoparticles. They then added another hydrated metal, ZrOCl2·8H2O, and TCPP (the organic linker) to the solution, washed with DMF solvent to dissolve the metals and linkers, and obtained their MOF: Fe3O4@MOF-545 with an average particle size of 1100nm.

Structure of a Zr-based MOF-545
Figure 1. Zr-based MOF-545. Adapted from 2024 Chen et al.

 

Next, they created a solution of their MOF, 4.2% sodium alginate, TEMED, and acrylamide to form the polyacrylamide hydrogel. The resulting solution was added drop-by-drop to a CaCl2 solution to form microspheres and stirred magnetically for an hour to obtain the MMOF hydrogel (magnetic MOF hydrogel). The researchers used scanning electron microscopy to characterize the MMOF hydrogel and found that the MMOF hydrogel had a microporous structure and clear surface grooves, enhancing its surface area and adsorptive capacity. (Figure 2)

Scanning electron microscopy of the MMOF hydrogel. The surface grooves and external and internal porous structure are visible.
Figure 2. (A) SEM image of MMOF hydrogel. (B-C) Notable grooves are seen on the surface of the MMOF hydrogel. Adapted from 2025 Cheng et al.

To confirm the heightened performance of the MMOF hydrogel, the researchers compared its dye adsorption and selectivity for MG dye compared to a magnetic hydrogel and a pure hydrogel.  The resulting MMOF hydrogel was found to be a significantly more effective adsorptive agent for MG dye than the other types of hydrogels (Figure 3), further showing the effectiveness of MOFs in increasing adsorption. The MMOF hydrogel also displayed enhanced selectivity to MG dye when applied to the surface of aquatic tissues in situ (Figure 4). 

 

Picture of hydrogel, MOF hydrogel, and MMOF hydrogel placed in solution containing MG dye. The container with MMOF hydrogel is the only one that became clear with no blue color left over, showing the higher adsorption rate of the MMOF hydrogel. The graph to the right of the image further supports this as MMOF hydrogel adsorption rate is over 90%.
Figure 3. Adsorption rate of MMOF hydrogel compared to magnetic hydrogel and hydrogel. MMOF hydrogel displayed greater MG dye adsorption than the magnetic hydrogel and hydrogel. Adapted from 2025 Cheng et al.

 

MMOF hydrogels placed on fish tissue with MG and other dyes on the surface. The hydrogels fully remove the MG dye.
Figure 4. MMOF hydrogel selectivity tested through application of fish tissue containing MG, acridine yellow, methylene blue, carmine, and crystal violet dyes. MMOF hydrogel shown to selectively remove MG dye from environment when in proximity to other dyes. Adapted from 2025 Cheng et al.

Cheng et al. then tested MMOF hydrogels with different characteristics to find material and environmental conditions for optimal adsorption. They found that sodium alginate concentration and MOF:hydrogel weight ratio were associated with the adsorptive capacity of the MMOF hydrogels. The optimal sodium alginate concentration was found to be 4.2%, and the optimal MOF:hydrogel weight ratio was found to be 12.

The researchers also tested the MMOF hydrogel in different environmental conditions to determine its limitations and where it performed best. They observed that the MMOF hydrogels showed the greatest adsorption at an MG dye concentration of 100mg/L (Figure 5A). This is due to the increased competition of MG molecules for adsorption sites on the surface of the MMOF hydrogel at higher concentrations. They also found that adsorption plateaued at MMOF hydrogel weight concentrations higher than 20mg/mL (Figure 5B) due to the adsorption sites on the hydrogel reaching equilibrium. Additionally, adsorption was highest at an MG solution pH of 6 (Figure 5C). At lower pH, H+ ions would compete with MG by due to the negatively charged functional group on the MMOF hydrogel. At higher pH, the carboxyl group on the MMOF hydrogel is ionized, decreasing the adsorption rate of MG dye. The adsorption rate of MG dye by the MMOF hydrogel was also found to show little decrease after 25 days of storage at 60ºC, indicating the strong stability of the material. 

Image containing Graphs A, B, C.A: Conc. vs adsorption rate. Adsorption rate peaks at conc of 100mg/L B: MMOF hydrogel weight concentration vs adsorption rate. adsorption rate peaks at 20mg/ml C: pH vs adsorption rate. Adsorption rate peaks at pH 6.
Figure 5. (A) MMOF hydrogel MG dye adsorption rate peaked at MG concentration of 100 mg/L. (B) Adsorption remains almost the same at MMOF hydrogel weight concentrations of 20mg/L and higher. (C) When the concentration of the MG solution is 100 mg/mL, the pH of the MG solution alters the adsorptive capacity of the MMOF hydrogel with the highest adsorption being observed at pH 6. Adapted from 2025 Cheng et al.

In their work, Cheng et al. have successfully created stable and easy-to-replicate MMOF hydrogels showing high adsorptive capacity and selectivity to MG dye for aquatic tissue in situ. The easily modifiable structure of MOFS also opens the door to the production of MMOF hydrogels selective to other dyes as well. This research has great potential applications for the pretreatment of aquatic products like fish before they reach the market. If automated and integrated into the screening processes of aquatic products, these MMOF hydrogels could strengthen quality control and increase the safety of products that are entering the market.

 

References

Chen, H., Brubach, J.-B., Tran, N.-H., Robinson, A. L., Ferdaous Ben Romdhane, Mathieu Frégnaux, Francesc Penas-Hidalgo, Solé-Daura, A., Mialane, P., Fontecave, M., Dolbecq, A., & Mellot-Draznieks, C. (2024). Zr-Based MOF-545 Metal–Organic Framework Loaded with Highly Dispersed Small Size Ni Nanoparticles for CO2 Methanation. ACS Applied Materials & Interfaces, 16(10), 12509–12520. https://doi.org/10.1021/acsami.3c18154

Cheng, L., Lu, Y., Li, P., Sun, B., & Wu, L. (2025). Metal–Organic Framework (MOF)-Embedded Magnetic Polysaccharide Hydrogel Beads as Efficient Adsorbents for Malachite Green Removal. Molecules, 30(7), 1560–1560. https://doi.org/10.3390/molecules30071560‌

Dutta, S., Adhikary, S., Bhattacharya, S., Roy, D., Chatterjee, S., Chakraborty, A., Banerjee, D., Ganguly, A., Nanda, S., & Rajak, P. (2024). Contamination of textile dyes in aquatic environment: Adverse impacts on aquatic ecosystem and human health, and its management using bioremediation. Journal of Environmental Management, 353(120103), 120103. https://doi.org/10.1016/j.jenvman.2024.120103‌

Zhou, H.-C., Long, J. R., & Yaghi, O. M. (2012). Introduction to Metal–Organic Frameworks. Chemical Reviews, 112(2), 673–674. https://doi.org/10.1021/cr300014x