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Director: Julia Y. Ljubimova, MD, PhD
Faculty members: Eggehard Holler, PhD; Hui Ding, PhD; Rameshwar Patil, PhD; José Portilla-Arias, PhD; Pallavi Gangalum, PhD; Szu-Ting Chou, PhD; Anna Galstyan, MD, PhD; and Helena Kozlova, MBA.
For more information on research conducted at the Nanomedicine Research Center, visit the Ljubimova Laboratory.
The Nanomedicine Research Center at the Cedars-Sinai Department of Neurosurgery was established in August 2011. Julia Ljubimova, MD, PhD, leads the nanomedicine research team that includes synthetic chemists, pharmacologists, molecular biologists, radiologists and clinical oncologists.
The main goal of the nanomedicine research team is to engineer and synthesize effective nanomedicines for imaging and treatment of primary and metastatic cancers, including brain gliomas and primary and metastatic (secondary) HER2-positive and triple negative breast and lung cancers, which are incurable with current therapy. These nanodrugs can be intravenously delivered across the blood-brain barrier (BBB) and have been shown to be effective in treating gliomas, as well as breast cancer and brain metastasis from primary lung and breast tumors in mice.
The Nanomedicine Research Center has been awarded $10.2 million by NIH/NCI grants for developing and establishing a novel class of anti-cancer imaging and treatment agents known as the Polycefin™ family, the latest evolution of molecular drugs designed to slow or stop cancers by blocking them in multiple ways. The ultimate goal is to bring these novel classes of imaging and treatment nanomedicines to the clinical practice.
Compared with conventional chemotherapy, the novel nanodrugs from the Polycefin family developed at the Cedars-Sinai Nanomedicine Research Center are more effective for treating experimental primary and secondary tumors by increasing the concentration of the anti-cancer drug directly at the tumor site while decreasing general toxicity and immunogenicity. By using the alternative nanodrug delivery mechanisms, scientists can aid in fighting the multidrug resistance that is the hallmark of cancer cells.
The new generation of nanomedicine imaging agents and drugs aim to
- Improve the pharmaceutical and pharmacological properties of anti-cancer drugs and imaging agents
- Increase therapeutic efficacy by drug delivery through a tissue- or cell-specific mechanism
- Deliver multiple types of therapeutics for combination therapy or detection of cancer
The nanodrugs are biodegradable and nontoxic for patients and are able to deliver multiple anti-tumor inhibitors simultaneously directly to cancer cells. In addition, nanodrugs prevent and/or overcome drug resistance and improve the efficacy of treatment, leading to improved quality of cancer patients' lives. Engineered drugs can be adapted for each cancer patient, with adjustments for individual tumor genome/proteome profiles for treatment of primary tumors and for patients' tumor progression.
Environmental nano pollution and its influence leading to the development of brain tumors and neurodegenerative disorders are under intensive investigation at the Nanomedicine Research Center.
The Nanomedicine Research Center is a part of the NIH/NCI Alliance for Nanotechnology in Cancer 2010–2015, which engages the nation's leading nanomedicine centers in a collaborative effort aimed at accelerating use of nanotechnology to advance cancer diagnosis, treatment and prevention.
Nanomedicine Research Center is multidisciplinary, combining collaborations across a number of departments at Cedars-Sinai, including:
- Surgery Department
- Department of Medicine
- S. Mark Taper Foundation Imaging Center
- Pathology and Laboratory Medicine
- Obstetrics and Gynecology Department
- Department of Biomedical Sciences
- Samuel Oschin Comprehensive Cancer Institute
- Division of Surgical Oncology at UCLA
- UCLA Molecular Biology Institute
- Department of Chemical Engineering at the Koch Institute of Integrative Cancer Research at MIT in Boston.
Through these collaborations, we are able to design drugs in the laboratory and test them on animal models.
Patil R, Ljubimov AV, Gangalum PR, Ding H, Portilla-Arias J, Wagner S, Inoue S, Konda B, Rekechenetskiy A, Chesnokova A, Markman JL, Ljubimov VA, Li D, Prasad RS, Black KL, Holler E, Ljubimova JY. MRI virtual biopsy and treatment of brain metastatic tumors with targeted nanobioconjugates. ACS Nano. 2015. [In press.]
Ding H, Patil R, Portilla-Arias J, Black KL, Ljubimova JY, Holler E. Quantitative analysis of PMLA nanoconjugate components after backbone cleavage. Int J Mol Sci. 2015;16(4):8607-8620. http://www.mdpi.com/1422-0067/16/4/8607.
Hsu BB, Jamieson KS, Hagerman SR, Holler E, Ljubimova JY, Hammond PT. Ordered and kinetically discrete sequential protein release from biodegradable thin films. Angew Chem Int Ed Engl. 2014 Jul 28;53(31):8093-8098. http://onlinelibrary.wiley.com/doi/10.1002/anie.201403702/abstract;jsessionid=DF6B56E755
Hsu BB, Hagerman SR, Jamieson K, Veselinovic J, O'Neill N, Holler E, Ljubimova JY, Hammond PT. Multilayer films assembled from naturally-derived materials for controlled protein release. Biomacromolecules. 2014 Jun 9;15(6):2049-2057. http://pubs.acs.org/doi/abs/10.1021/bm5001839.
Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Black KL, Chakravarty D, Sanborn JZ, Berman SH, Ljubimova JY, et al; TCGA Research Network. The somatic genomic landscape of glioblastoma. Cell. 2013 Oct 10;155(2):462-477. http://www.cell.com/cell/abstract/S0092-8674(13)01208-7.
Ljubimova JY, Ding H, Portilla-Arias J, Patil R, Gangalum PR, Chesnokova A, Inoue S, Rekechenetskiy A, Nassoura T, Black KL, Holler E. Polymalic acid-based nano biopolymers for targeting of multiple tumor markers: an opportunity for personalized medicine? J Vis Exp. 2014 Jun 13;(88). http://www.jove.com/video/50668/polymalic-acid-based-nano-biopolymers-for-targeting-multiple-tumor.
Ljubimova JY, Portilla-Arias J, Patil R, Ding H, Inoue S, Markman JL, Rekechenetskiy A, Konda B, Gangalum PR, Chesnokova A, Ljubimov AV, Black KL, Holler E. Toxicity and efficacy evaluation of multiple targeted polymalic acid conjugates for triple-negative breast cancer treatment. J Drug Target. 2013 Dec;21(10):956-967. http://informahealthcare.com/doi/abs/10.3109/1061186X.2013.837470.
Ljubimova JY, Kleinman MT, Karabalin NM, Inoue S, Konda B, Gangalum P, Markman JL, Ljubimov AV, Black KL. Gene expression changes in rat brain after short and long exposures to particulate matter in Los Angeles basin air: comparison with human brain tumors. Exp Toxicol Pathol. 2013 Nov;65(7-8):1063-1071. http://www.sciencedirect.com/science/article/pii/S0940299313000547.
Ding H, Helguera G, Rodríguez JA, Markman J, Luria-Pérez R, Gangalum P, Portilla-Arias J, Inoue S, Daniels-Wells TR, Black K, Holler E, Penichet ML, Ljubimova JY. Polymalic acid nanobioconjugate for simultaneous immunostimulation and inhibition of tumor growth in HER2/neu-positive breast cancer. J Control Release. 2013 Nov 10;171(3):322-329. http://www.sciencedirect.com/science/article/pii/S0168365913003350.
Markman JL, Rekechenetskiy A, Holler E, Ljubimova JY. Nanomedicine therapeutic approaches to overcome cancer drug resistance. Adv Drug Deliv Rev. 2013 Nov;65(13-14):1866-1879. http://www.sciencedirect.com/science/article/pii/S0169409X13002329.
Ljubimova JY, Holler E. Biocompatible nanopolymers: the next generation of breast cancer treatment? Nanomedicine (Lond.) 2012 Oct;7(10):1467-1470. http://www.futuremedicine.com/doi/abs/10.2217/nnm.12.115.
Patil R, Portilla-Arias J, Ding H, Konda B, Rekechenetskiy A, Inoue S, Black KL, Holler E, Ljubimova JY. Cellular delivery of doxorubicin via pH-controlled hydrazone linkage using multifunctional nano vehicle based on poly(β-L-malic acid). Int J Mol Sci. 2012;13(9):11681-11693. http://www.mdpi.com/1422-0067/13/9/11681.
Inoue S, Patil R, Portilla-Arias J, Ding H, Konda B, Espinoza A, Mongayt D, Markman JL, Elramsisy A, Phillips HW, Black KL, Holler E, Ljubimova JY. Nanobiopolymer for direct targeting and inhibition of EGFR expression in triple negative breast cancer. PLOS One. 2012;7(2):e31070. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0031070.
Inoue S, Ding H, Portilla-Arias J, Hu J, Konda B, Fujita M, Espinoza A, Suhane S, Riley M, Gates M, Patil R, Penichet ML, Ljubimov AV, Black KL, Holler E, Ljubimova JY. Polymalic acid-based nanobiopolymer provides efficient systemic breast cancer treatment by inhibiting both HER2/neu receptor synthesis and activity. Cancer Res. 2011 Feb 15;71(4):1454-1464. http://cancerres.aacrjournals.org/content/71/4/1454.
Ding H, Inoue S, Ljubimov AV, Patil R, Portilla-Arias J, Hu J, Konda B, Wawrowsky KA, Fujita M, Karabalin N, Black KL, Holler E, Ljubimova JY. Inhibition of brain tumor growth by intravenous poly(-L-malic acid) nanobioconjugate with pH-dependent drug release. Proc Natl Acad Sci USA. 2010 Oct;107(42):18143-18148. http://www.pnas.org/content/107/42/18143.