Immunogenic Lipid Encapsulated Mesoporous Silica Nanoparticles for Ovarian Cancer Immunotherapy

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