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Nanomedicine-Immunology and Molecular Biomedical Research (NLIMBR)

Associate Professor Jagat Kanwar, group leader of the Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research in Nanomedicine (LIMBR-setup in 2007 after A/Prof. Kanwar's movement to Deakin University), has a national and international reputation in investigating fundamental and applied molecular aspects of cancer and chronic inflammation. The group carries out research in the areas of national priority such cancer, chronic inflammatory diseases (ageing) and molecular nutrition (complementary alternative medicine) with milk/herbs bioactives as immunomodulators. Additionally by investigating bioactives' role in gut biology, and immune health, LIMBR seeks to commercially exploit dairy bioactives for human health and the development of functional food ingredients, health supplements and neutraceutical and/or pharmaceutical grade immunotherapeutics. Apart from industry funded projects our research is also focused on siRNA, miRNA, aptamer, and immunoliposomes technology and disease target drug discovery. LIMBR provides high quality research training and education to undergraduate and postgraduate students which, in turn, strengthen Deakin's strategic research and academic priorities, helping our students keep in pace with the emerging concepts of science and technology.

An immense focus of the group is to develop non-conventional therapeutics involving natural compounds for cancer and other inflammatory diseases. Nanomedicine is the need for the day to develop, synthesise and characterize of nanoformulations that can achieve a more targeted and specific delivery system is being carried out in the laboratory. Extensive research is carried out for development and physico-chemical characterization of biodegradable and biocompatible drug delivery vehicles. Novel targeted delivery systems possessing enhanced permeation retention effect, narrow size range and stable have been successfully synthesised. A number of other developments including microfluidics, nanodevices and microchips for targeted delivery and diagnosis are also our major interests. The principle aim is to achieve a system where there is a diagnostic and therapeutic approach to target cancer and other inflammatory conditions. Recently microfluidic systems being worked upon are targeting an approach to less time consuming and more economic methods for cancer and microbial infection diagnosis.

Current Research

We seek to explore the roles of molecular mediators, antioxidants and cellular communication in the pathophysiological mechanisms of chronic inflammatory, microbial diseases and cancer. LIMBR focuses on the:

1. Development of multi-targeted oral or intravenous delivery systems for treatment and diagnosis:

• cancer and chronic inflammatory diseases targeted nanomedicine based drug delivery
• siRNA, miRNA anti-sense targeted gene nanomedicine based technology to target cancer and inflammation
• drug discovery with anticancer targets for cancer cell survival, death, arrest, and repair
• development of recombinant proteins and searching new immunomodulatory and anti-inflammatory bioactives, proteins and peptides for cancer and neuroprotection
• development of complementary alternative medicine from the milk derived proteins including metal binding protein (Lactoferrin), and herbal preparation derived active components with a special focus on the treatment of colon and breast cancers
• development of oral and intravenous administration of nanocarriers to overcome the challenging concept of drug resistance in various cancers
• development of new generation safe, biodegradable, less toxic, disease targeted natural contrast materials for imaging

Our research combines Immunology with state of the art and cutting edge techniques in Molecular Biology, Biochemistry, Nanobiotechnology and visualization to investigate the pathways in which key molecules are regulated in both normal and disease states. A number of in vitro human cell/tissue based co-culture models for cancers, microbial infections; chronic inflammatory diseases (osteoarthritis, inflammatory bowel disease), gut health, neurodegeneration and immunomodulation have been developed. Our objective is to understand and target the mechanisms involved at the molecular and sub cellular level which gives us an edge over the prevalent targeting techniques. We carry out both academic and commercial research projects and develop new approaches for the diagnosis, treatment, and nanomedicine based new generation delivery systems for the prevention of human diseases like cancer, infectious, inflammatory bowel disease (IBD), neurodegenerative, osteoarthritis, cardiovascular and pulmonary diseases. LIMBR through national and international collaborations aims in near future to translate discoveries into new approaches for the diagnosis, treatment, and prevention of human diseases.

Our recent research focus on locked nucleic acid (LNA) LNA-modified aptamers conjugated "double targeted nano-bullet nanocapsules" with natural anti-tumour proteins which specifically target cancer cells. We are developing natural nano-medicinal based war against cancer cells with double targeted nano-bullet nanocapsules that specifically induce their traumatic death and spare normal body cells. The success behind our team is, working as a unit in creating and maintaining a healthy and work friendly environment.

2. Novel nano-medicinal based vaccines and immunotherapy:

Our interests also focus on development and loading of nano materials like silk, oxides of iron, gold and ceramics which are routinely characterised by powder XRD, SEM, TEM, FT-IR, for their magnetic susceptibility and N2 adsorption-desorption. We are interested in developing novel nano-carriers such as quantum dot bio-conjugate libraries for multiplexed bio-sensing, proteomics, cellular and tissue imaging and drug delivery. Our research interests focus on the development of novel nanodevices or nanotechnology for medical applications for stem cell tracking and overcoming multidrug resistance (MDR) of cancer. These novel disease targeted nanocarriers designed for diverse applications in vaccines, immunotherapy, and drug delivery of protein or peptide antigens immunostimulatory ligands to dendritic cells and subsequent stimuli to T- lymphocytes, B-lymphocytes and TH17 cells. Our research seeks novel nanomaterials and multifunctional nanotechnologies in order to develop advanced targeted drug delivery systems with highly interdisciplinary and translational research.

3. Micro-fluidics and Lab-on-a-Chip devices for delivery and diagnosis:

Recently our group is focused on exploiting various Lab-on-a-Chip, or Microfluidic devices used in biomedical diagnostics and develop knowledge for fundamental research in microfluidic and nanofluidic phenomena and in the clinic for differential diagnosis and personalized treatment of complex human diseases including cancer, infectious, inflammatory bowel disease (IBD), neurological diseases, osteoarthritis, cardiovascular and pulmonary diseases.

Group members

AProf. Jagat Kanwar
Dr. Rupinder Kanwar

VNL Ganesh Mahidhara
Isha Gupta
Yogesh Patel
Rasika Samarasinghe
Sishir Kumar Kamalapuram
Nihal Ganesh Maremanda
Kislay Roy
Bhasker Sriramoju
Nithya S

Selected publications:

1. Kanwar JR, Roy K, Kanwar RK. (2011) Chimeric aptamers in cancer cell-targeted drug delivery. Critical Reviews in Biochemistry and Molecular Biology, 2011 (In Press). Top 5% in the field
2. Kanwar JR, Mohan, Rajiv R., Vasu P, Bhasker R, Kanwar, Rupinder K. Nanoparticles in the treatment and diagnosis of neurological disorders: Untamed dragon with fire power to heal. Nanomedicine: Nanotechnology, Biology, and Medicine. Accepted 11 June 2011. Top 5% in the field
3. Kanwar, Jagat R., Mahidhara, Ganesh and Kanwar, Rupinder K. (2011) Anti-angiogenic therapy using nanotechnological based delivery system, Drug Discovery Today, 2011 Mar;16(5-6):188-202. Top 5% in the field
4. He, Shu-Ming, Li, Songshu, Kanwar, Jagat R. and Zhou, Shu-Feng. (2011) Structural and functional properties of human multidrug resistance protein 1 (MRP1/ABCC1), Current Medicinal Chemistry, 18(3):439-81. Top 5% in the field
5. Baratchi, Sara, Kanwar, Rupinder K. and Kanwar, Jagat R, (2010) Survivin: a target from brain cancer to neurodegenerative disease. Critical Reviews in Biochemistry and Molecular Biology, 2010-12, 45(6): 535-554. Top 5% in the field
6. Kanwar, Jagat R., Kamalapuram, Sishir K. and Kanwar, Rupinder K. (2010) Targeting survivin in cancer: patent review. Expert Opinion on Therapeutic Patents, 2010-12, 20(12): 1723-1737
7. Li, Hali, Tan, Gang, Jiang, Xiang, Qiao, Haiquan, Pan, Shanghua, Jiang, Hongchi, Kanwar, Jagat R. and Sun, Xueying. (2010) Therapeutic effects of matrine on primary and metastatic breast cancer, The American Journal of Chinese Medicine, 2010-12, 38(6): 1115-1130. Top 5% in the field
8. E Giuliano, BW Yarnall, R Gupta, B Dylan, JR Kanwar, (2011) Mitomycin C: A promising agent for the treatment of canine corneal scarring, Veterinary Ophthalmology, Article first published online: 18 APR 2011
9. Burrow H, Kanwar RK, Kanwar JR, (2011) Design antioxidant enzyme activities of iron saturated bovine lactoferrin (Fe-blf) in human gut epithelial HT29 cells under oxidative stress, Medicinal Chemistry, May 1; 7(3):224-30.
10. Kanwar JR, Neha Singh, and Kanwar RK. (2011) Role of nanomedicine in reversing drug resistance mediated by ATP binding cassette transporters and p-glycoprotein in melanoma. Nanomedicine London UK. 6(4): 701-714. Top 5% in the field
11. Kanwar JR, Benjamin ML and Kanwar RK. (2011) The use of cyclodextrins nanoparticles for oral delivery. Current Medicinal Chemistry. 18(14):2079-85. Top 5% in the field
12. Baratchi, S, Kanwar RK, Kanwar JR. (2011) Survivin Mutant Protects Differentiated Dopaminergic SK-N-SH Cells Against Oxidative Stress. PLosOne, Jan 10; 6(1):e15865
13. Kanwar JR, Sishir KK and Kanwar RK. (2011) Targeting survivin in cancer: cell signalling perspective. Drug Discovery Today. Jun; 16(11-12):485-94. IF: - 6.63, Top 5% in the field, Journal class:A
14. Kanwar, Jagat R., Mohan, Rajiv R., Kanwar, Rupinder K., Roy, Kislay and Bawa, Raj. (2010) Applications of aptamers in nanodelivery systems in cancer, eye and inflammatory diseases, Nanomedicine, 2010, 5(9): 1435-1445. Top 5% in the field
15. Cheung CHA, Sun X, Kanwar JR, Bai JH, Cheng LT and Krissansen GW. (2010) A cell-permeable dominant-negative survivin protein induces apoptosis and sensitizes prostate cancer cells to TNF-alpha therapy. Cancer Cell International, 28/10/2010, 10(1): 43. IF: - 2.03
16. Baratchi, Sara, Kanwar, Rupinder K. and Kanwar, Jagat R. (2011) Novel survivin mutant protects differentiated SK-N-SH human neuroblastoma cells from activated T-cell neurotoxicity. Journal of Neuroimmunology, 2011 Apr; 233(1-2):18-28.. IF: - 2.841. Journal class:- B.
17. Baratchi, Sara, Kanwar, Rupinder K., Cheung, Chun Hei Antonio and Kanwar, Jagat R. (2010) Proliferative and protective effects of SurR9-C84A on differentiated neural cells. Journal of Neuroimmunology, 8/10/2010, 227(1): 120-132, IF: - 2.841. Journal class: - B
18. Kanwar, R. K., Cheung, C. H., Chang, J. Y. and Kanwar, J. R. (2010) Recent advances in anti-survivin treatments for cancer. Current Medicinal Chemistry, 1/05/2010, 17(15): 1509-1515. Top 5% in the field
19. Cheung CH, Chen HH, Cheng LT, Lyu KW, Kanwar JR, Chang JY. (2010) Targeting Hsp90 with small molecule inhibitors induces the over-expression of the anti-apoptotic molecule, survivin, in human A549, HONE-1 and HT-29 cancer cells. Mol Cancer. Apr 15; 9:77
20. Jiang H, Tao W, Zhang M, Pan S, Kanwar JR, Sun X. (2010). Low-dose metronomic paclitaxel chemotherapy suppresses breast tumours and metastases in mice. Cancer Invest. 2010 Jan; 28(1):74-84
21. Kanwar JR, Mahidhara G and Kanwar RK. Recent advances in nano- technology for drug delivery to the brain. Current Nanoscience. 2009. Accepted, in press. (Impact factor: =2.9).
22. Baratchi S, Kanwar RK, Khoshmanesh K, Vasu P, Chauhan A, Hittu M, Parratt A, Krishnakumar S, Sun X, Sahoo SK and Kanwar JR. Promises of Nanotechnology for Drug Delivery to Brain in Neurodegenerative Diseases. Current Nanoscience. 2009 5(1): 15-25. (Impact factor: =2.9).
23. Kanwar JR, Palmano KP, Sun X, Kanwar RK, Gupta R, Haggarty N, Rowan A, Ram S, Krissansen GW. (2008) 'Iron-saturated' lactoferrin is a potent natural adjuvant for augmenting cancer chemotherapy. Immunol Cell Biol. 86(3):277-288
24. Krissansen GW, Singh J, Kanwar RK, Leung, E, Lehnert KB, Kanwar JR and Yang Y (2006).A psuedosymmetric cell adhesion regulatory domain in the ß7 tail of integrin a4ß7. European Journal of Immunology 36(8): 2203-2214
25. Kanwar JR, Kanwar RK and Krissansen GW (2004). Simultaneous neuroprotection and blockade of inflammation reverses autoimmune encephalomyelitis. Brain 127:1313-1331
26. Sun X, M Vale, E Leung, Kanwar JR et al (2003). Mouse B7-H3 induces antitumor immunity. Gene Therapy 10: 1728-1734
27. Kanwar JR, Shen W, Kanwar RK, Berg RW and Krissansen GW (2001) Effect of survivin antagonists on the growth of established tumors and B7-1 immunogene therapy. Journal of The National Cancer Institute 93 (20): 1541-1552.
28. Kanwar JR, Kanwar RK, Pandey S, Ching LM and Krissansen GW(2001). Vascular attack by 5,6-dimethylxanthenone-4-acetic acid combined with B7.1 (CD80)-mediated immunotherapy overcomes immune resistance and leads to the eradication of large tumors and multiple tumor foci. Cancer Research 61(5): 1948-1956. (Impact factor: 8.3; 31 citations
29. Kanwar RK, Kanwar JR, Wang D, Ormrod D and Krissansen GW (2001). Temporal expression of heat shock proteins 60 and 70 at lesion-prone sites during atherogenesis in the ApoE-deficient mice. Arteriosclerosis Thrombosis and Vascular Biology 21 (12): 1991-1997
30. Kanwar JR, Harrison JEB, Wang D, Leung E, Mueller W, Wagner N and Krissansen GW (2000). ß7 integrins contribute to demyelinating disease of the central nervous system. Journal of Neuroimmunology 103 (2). 146-152

Patents:

Web link: http://www.wipo.int/pctdb/en/
(search for "Applicant name" Jagat Kanwar/Rupinder Kanwar)

1. WO2006/054908
2. WO 2008/140335
3. WO 2008/079030
4. WO 2000/076497
5. WO 2002/030447
6. WO 2002/030448
7. WO 2004/009131
8. WO 2007/055599
9. WO 2006/112739
10. WO 2006/112738
11. WO 2005/107736