Immunogenic Lipid Encapsulated Mesoporous Silica Nanoparticles for Ovarian Cancer Immunotherapy

2017 NSMS Research Experience for Undergraduates

UNM| May 30^th-August 4^th

Immunogenic lipid encapsulated mesoporous silica nanoparticles for Ovarian Cancer Immunotherapy

Karen Sanchez[1], C. Jeffrey Brinker[2]^,3, and Rita E. Serda*[3]

Department of Chemical and Materials Engineering, New Mexico State University, Las Cruces, New Mexico, 88003, NSF/UNM Center for Micro-Engineered Materials, Department of Chemical and Biological Engineering, The University of New Mexico, Albuquerque, New Mexico 87131

Email: ritaserda@unm.edu

Introduction

     Traditional cancer treatments expose the entire body to high levels of toxic agents causing adverse side effects. The goal of immunotherapy is to increase specificity to cancer cells by eliciting an immune response against the abnormal cells. This study evaluated mesoporous silica nanoparticles (MSNs) and lipid-coated mesoporous silica nanoparticles (LC-MSN) as delivery vehicles for vaccine development. The nanoparticles were loaded with the model antigen ovalbumin and monophosphoryl lipid A (MPL-A) to both direct the immune response and activate dendritic cells (DC). The nanoparticles were compared based on cellular uptake, activation, and antigen processing and presentation by DC. DC, the most potent antigen presenting cells, were derived from bone marrow extracted from C57BL/6 mice. Flow cytometry was used to confirm DC phenotype (CD11c+), measure activation (CD86 expression), and evaluate presentation of the ovalbumin peptide SIINFEKL in association with H-2K^b. Confocal and scanning electron microscopy were used to visualize association of DC and nanoparticles.

Results and Discussion

     This study determined the effectiveness of ovalbumin loading in MSN and LC-MSN and the ability of DC to process and present the delivered antigen. PLC-MSNs and MSNs were loaded with a mass ratios of silica cores to ovalbumin of 4:1 and 10:1. The CBQCA assay was used to quantitate protein loading and the resulting LC-MSNs and MSNs were added to plated DCs. 72 hours later, the cells were collected and analyzed using a flow cytometer. LC-MSNs proved to be more effective than the pure MSN with respect to both loading of the ovalbumin and for processing and presentation of the antigen.

     DCs treated with LC-MSNs for either 30 minutes or 120 minutes were visualized using confocal microscopy. Images acquired on the Zeiss confocal microscope supported internalization of the nanoparticles by the DC, with intracellular trafficking of the nanoparticles along the microtubules to the perinuclear region of the cell.

Conclusion

     LC-MSNs were more effective than MSN for both loading the ovalbumin antigen and for processing and presentation of the antigen by DC.

References

(1.) Chiang, Cheryl Lai-Lai., Kandalaft, Lana E., (September 1, 2013). A Dendritic Cell Vaccine Pulsed with Autologous Hypochlorous Acid-Oxidized Ovarian Cancer Lysate Primes Effective Broad Antitumor Immunity: From Bench to Bedside. NIH Public Access.

(2.) Dunfee, Paul N., Lin, Yu-Shen., Dunphy, Darren R., (July 15, 2016). Mesoporous Silica Nanoparticle-Supported Lipid Bilayers (Protocells) for Active Target and Delivery to Individual Leukemia Cells., ACS NANO. 10, 8325- 8345

(3.) Slutter, Bram., Zhi, Ding., Bouwstra, Joke A., Bal, Suzzane., Jiskoot, Wim., Adjuvant effect of cationic liposomes and CpG depends on administration route.

(4.) Wang, Min., Zander, Thomas., Liu, Xiaoyan., Liu, Chao.,(2015). The effect of temperature on supported dipalmitoylphosphatidylcholine (DPPC) bilayers: Structure and lubrication performance. Journal of Colloid and Interface Science, 445, 84-92

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[1] Department of Chemical and Materials Engineering, New Mexico State University

[2] Center for Micro-Engineered Materials, The University of New Mexico

[3] Department of Chemical and Biological Engineering, The University of New Mexico