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Developing Bio-mimetic neutrophil coated nanoparticles as a potential targeted treatment module for arthritic diseases
Korea (KMSA) - KyungHee University, Seoul
Depart. Of Clinical Pharmacology & Therapeutics
Sung Vin Yim
Type of Research Project
- Basic science
What is the background of the project?
Neutrophils are the primary responders of most inflammatory reactions and play a pivotal role in perpetuating the inflammatory reaction but also in inhibiting inflammation. ➢ Essentially, there is a lack of targeted treatment that can effectively modulate neutrophil mediated disease progression with high efficacy and reduced toxicity. ➢ There has been a steep increase among the researchers to investigate the therapeutic potential of nanoparticles in different disease conditions. A number of nano-formulated drugs have also been FDA approved and are in clinical practice. ➢ The use of cell-membrane camouflaged nanoparticles, inspired by the biomimetic strategy. These biomimetic nanoparticles can take advantage of the natural properties of various cells thereby enhancing the therapeutic efficacy of nanomedicine. ➢ The concept involves disguising a nanoparticle with a cell membrane decorated with functional proteins that allow the nanoparticle to actively take part in the physiological processes via multiple regulatory pathways.
What is the aim of the project?
The main goal of this research project is to develop biologically derived semi-synthetic neutrophil coated nanoparticle therapeutics that combine the benefits of both man-made and natural materials for the effective treatment of arthritis.
What techniques and methods are used?
1. To synthesize neutrophil coated nanoparticles Poly dl-lactic-co-glycolic acid (PLGA) core will be synthesized using sonication method. Neutrophil membranes will be derived by hypotonic treatment of neutrophils isolated from peripheral blood of mice. 2. To assess the stability and characterize the synthesized neutrophil nanoparticles The stability of synthesized neutrophil coated nanoparticles will be assessed in a time dependent manner using spectrophotometric methods. Characterization of the synthesized neutrophil nanoparticles will be based on examining the morphology, size and charge of the synthesized neutrophil nanoparticle determined by using Dynamic light scattering analysis (DLS) and Transmission electron microscopy (TEM) 3. To investigate the safety and efficacy of neutrophil nanoparticles and the interaction binding efficiency to target cells (in vitro) To achieve this aim, the neutrophil nanoparticles will be tested for toxicity in different cell types using appropriate cell viability assays. Different cells will be cultured in vitro and the interaction potential of neutrophil nanoparticles will be tested at different concentrations. The effect of the neutrophil coated nanoparticles on cell differentiation and cell proliferation will be tested to determine specificity of targeted delivery. These tests will be performed a series of times to eliminate cross reactive interactions. 4. To investigate the targeted delivery and anti-inflammatory effects of neutrophil nanoparticles in different in vivo model of inflammatory arthritis. To achieve his aim, the therapeutic efficiency of the neutrophil nanoparticles will evaluated in in-vivo models of inflammatory arthritis like Tg86(A) mice (transgenic model of ankylosing spondylitis), CIA (animal model for Rheumatoid arthritis) and SKG mice (transgenic model of spondyloarthritis). Based on the data obtained the signaling pathway will be identified.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
- The tasks of the student will be performed on his/her own
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
● The students are expected to rerad up on the background of the project and be able to understand the concepts clearly. ● Students are expected to be involved in the synthesis of nanoparticles with consistent reproducibility. ● Students are expected to analyze the stability of the synthesized nanoparticles using dynamic light scattering and zeta potential analyzers. ● Students are expected to be able to handle mice and isolate neutrophils from peripheral blood and subsequently derived neutrophil membrane by hypontonic treatment. ● Students are expected to examine the efficiency of neutrophil nanoparticles in different mouse model systems using polymerase chain reaction and western blot. They will invesitgate the expression of inflammatory markers in comparison to disease model. ● The students are expected to analyse the data and summarize the data with figure illustrations. ● The students are expected to present the data obtained from the experiments in front of lab members at regular intervals. ● The students are expected to actively parpticipate in lab meetings and par take in discussion and ask questions pertaining to the research work.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
● Students will have guidance from the tutor for carrying out relevant literature survey. ● Regular lab meetings are conducted which will enable the students to have discussions and ask questions related to the research work. ● Students will have the oppurtunity to participate in and give presentations during department meetings and seminars.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a scientific report
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
The student should be accustomed to handling mice for the experiments. The students should be motivated and have keen interests in contributing to doing good research.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- Y. Zhai; J. Su; W. Ran; P. Zhang; Q. Yin; Z. Zhang; H. Yu; and Y. Li; “Preparation and Application of Cell Membrane-Camouflaged Nanoparticles for Cancer Therapy.;” Theranostics; vol. 7; no. 10; pp. 2575–2592; 2017.
- Q. Zhang; D. Dehaini; Y. Zhang; J. Zhou; X. Chen; L. Zhang; R. H. Fang; W. Gao; and L. Zhang; “Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis.;” Nat. Nanotechnol.; vol. 13; no. 12; pp. 1182–1190; Dec. 2018
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