Investigating a Hybrid Nanoparticle System for DVT Treatment and Detection

Transcription

1 Investigating a Hybrid Nanoparticle System for DVT Treatment and Detection Thousand Oaks High School AP Research STEM

2 1 Introduction 2

3 Background Blood clot formation Prone to leg, thigh, pelvis Ability to travel Figure 1: Illustration of a thrombus formation within the major artery of the heart. 3

4 Population affected by DVT 2 million a year in U.S. alone 60, ,000 die related to VE All ethnicities, both genders, all ages groups 4

5 Symptoms - Edema - Swelling - Varicose veins - Discoloration Figure 2. Common symptoms of DVT 5

6 Current Treatments Basic - Lifestyle modifications - Mechanical compression Experimental - Anticoagulant therapy - Inferior vena cava filter 6

7 Disadvantages of Current Treatments - Improper clot clearance - Hemorrhage occurrence - Bleeding in other organs/tissues - Fainting 7

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9 Classification of Nanoparticles Organic - Based off organic molecules - Including CNTs, liposomes, dendrimers Inorganic - Cores consist of metals and metal oxides 9

10 Classification of Nanoparticles Figure 4. Display of organic and inorganic nanoparticle and a schematic representation of typical nano cores for the construction of radiolabeled nanoparticles. 10

11 Nanoparticle Advantages Size - Ability to travel through microscopic blood vessels Imaging - Visualization through ultrasound Accuracy - Specific targeted drug delivery system 11

12 PPACK Nanoparticles - Phe[D]-Pro-Arg-Chloromethylketone - Selective and irreversible inhibitor of thrombin - Can be attached to core of nanoparticle 12

13 Biomarkers C-reactive protein D-dimer Wells Score 13

14 Soluble P-selectin (spsel) - An adhesion glycoprotein - Present in α Granules - Mediator of platelet-leukoc yte interactions Figure 5. Role of P-Selectin linking inflammatory and thrombotic pathophysiological pathways at the arterial vessel wall 14

15 Purpose - Increase efficiency of thrombin removal - Allow diagnosis of acute thrombus formation 15

16 Research Question Is it possible to implement PPACK NPs as a treatment option for DVT and use spsel as a biomarker for acute thrombus formation? 16

17 Hypothesis Alternate: Nanoparticles can be applied for thrombus removal as well as spsel be used as a biomarker for DVT. Null: Nanoparticles cannot be applied for thrombus removal and spsel cannot be used as a biomarker due toxicity and inaccuracy 17

18 Methods 18

19 Process Step 1 Step 2 Step 3 Step 4 Step 5 Systematic Literature Review Selection Criteria Accumulated data on clinical trials Conclusions Discussions Implications Discuss results and communicate findings 19

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21 Data Collection Twelve Studies Patients Analyzed Biomarkers Avg. values of - DVT spsel: Wells Score: CRP: (μg/ml) D-dimer: ng/ml P-values spsel: Wells Score: CRP: D-dimer: Avg. values of + DVT 21

22 Results 22

23 PPACK NPs on Occlusion Time 23

24 spsel Concentrations 24

25 D-dimer Concentrations 25

26 C-reactive Protein 26

27 Wells Score 27

28 Discussion 28

29 PPACK Efficiency - Longest occlusion time - Connected covalently to NP surface - Kinetic advantage 29

30 Detection of Thrombus by spsel - Mediator of platelet-leukocyte and leukocyte interactions - Accumulation of fibrin Figure 6. Cell cell interactions mediated by P-selectin and PSGL-1. 30

31 Limitations - Ultrafine particles (UFPs) - Phagocytosis - Number of experiments on PPACK NPs on occlusion time 31

32 Conclusion - PPACK NPs can increase efficiency of thrombin removal - spsel can be used as most viable biomarker for DVT - Allows acute detection of thrombus formation 32

33 Further Work - Larger sample size studied - Risk of NP toxicity - Oxidative stress paradigm 33

34 Acknowledgements - Dr. Jennifer Stevenson - Dr. Nikki Malhotra - Dr. Alice Cho - Michelle Magnusson 34

35 References Angelini, D., Stabler, C., Hawley, A., Guire, K., Myers, D., Blackburn, S., Wakefield, T., & Sood, S. (2014) Soluble P-selectin and age adjusted D-dimer as predictive biomarkers of venous thrombosis. Blood 2014, 124:2853; retrieved from Ay, C. Simanek, R., Vormittag, R., Dunkler, D., Alguel, G., Koder, S., Kornek, G., Marosi, C., Wagner, O., Zielinski, C., & Pabinger, I. (2008). High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the vienna cancer and thrombosis study (CATS). Blood 2008, 112: Doi: CDC. (2015). Venous Thromboembolism (Blood Clots) Data and statistics. Retrieved from Entezari-Maleki, T., Talasaz, A., Salarifar, M., Hadjibabaie, M., Javadi, R., Bozorgi, A., Jenab, Y., Boroumand, M., & Gholami, K. (2013). Plasma vitamin D and its correlation with risk factors of thrombosis, P-selectin, and hs-crp level in patients with venous thromboembolism; the first study of iranian population. Iranaian Journal of Pharmaceutical Research (2014), 13(1): Retrieved from Fernando, A., & Angiolilo, D. (2013). Targeting P-selectin during coronary interventions. Journal of American College of Cardiology 61(20), Doi: /j.jacc Gremmel, T., Ay, C., Seidinger, D., Pabinger, I., Panzer, S., & Koppensteiner, R. (2011). Soluble p-selectin, D-dimer, and high-sensitivity C-reactive protein after acute deep vein thrombosis of the lower limb. Journal of Vascular Surgery 54(6), 48S-55S. doi: /j.jvs Hameed, A., Rubab, Z., Abbas Rizvi, S., Hussain, S., Latif, W., & Mohsin, S. (2017) Levels of platelet-derived microparticles and soluble p-selectin in patients of acute myocardial infarction (case control study). Journal of Pakistan Medical Association. Jul;67(7): Retrieved from Jungbauer, L., Ay, C., Sailer, T., Tengler, T., Koder, S., Kaider, A., Panzer, S., Quehenberger, P., Pabinger, I., & Mannhalter C. (2007). High concentrations of soluble P-selectin are associated with risk of venous thromboembolism and the P-selectin Thr715 variant. Clinical Chemistry 53:7, Doi: /clinchem Modi, S. Deisler, R., Gozell, K., Reicks, P., Irin, E., Brunsvold, M., Banton, K., & Beilman, G. (2016). Wells criteria for DVT is a reliable clinical tool to assess the risk of deep venous thrombosis in trauma patients. World Journal of Emergency Surgey: WJES, 11, 24. Doi: /s

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37 Investigating a Hybrid Nanoparticle System for DVT Treatment and Detection