Phospholipids as metastases-targeting molecules using barcoding as a new research tool in liposome discovery

Prof. Dr. A. Schroeder1), Technion – Israel Institute of Technology/Israel

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1.

Prof. Dr. Avi SchroederDepartment of Chemical Engineering, Technion – Israel Institute of Technology, Haifa, Israel

People involed

Dr Jeny Shklover (PhD - senior researcher; PRC) - Technion, Haifa, Israel (jenysh@technion.ac.il)

Mor Sela (MSc student of chemical engineering; PRC) - Technion, Haifa, Israel (mor.sela@campus.technion.ac.il)

Hadar Meltzer (BSc student of chemical engineering; PRC) - Technion, Haifa, Israel (hadarmeltzer@campus.technion.ac.il)

Yael Shammai (BSc student of chemical engineering; PRC ) - Technion, Haifa, Israel (yael.shammai@campus.technion.ac.il)

Abstract

In nature, biological membranes consist of more than fifty percent of (phospho)lipids. These lipids play a central role in cell-cell interactions and tissue recognition. Despite their important biological role, drug delivery systems seldom take advantage of the lipid profile to improve targeting. In fact, in most cases proteins or sugar groups conjugated to the surface of lipid-based drug delivery systems are used to modulate cell uptake and biodistribution. In preliminary studies, we found that the lipid profile of liposomes is extremely important for determining the biological fate of liposomes to cells of breast cancer. In this project, we will study how lipids can be used to control tissue distribution, specifically to sites of breast cancer metastases in mice.

A combinatorial barcoding apparatus will be employed to study the biological fate of an array of liposomes to triple negative breast cancer metastasis. We expect that the study will generate fundamental insights into the interaction of lipids with biological tissues at the cellular and whole-body level.

Benefit for the community

This multidisciplinary research program combines approaches from life sciences, material engineering, and medicine to advance our therapeutic capabilities. This program will make scientific, clinical and social impact, yielding significant progress in the fields of Cancer Medicine basic research and application, and Lipid Nanotechnology, and by providing industry with new lipid particle fabrication capabilities.

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Contact

Publications derived from the project:
1.
Zinger A, Koren L, Adir O, Poley M, Alyan M, Yaari Z, Noor N, Krinsky N, Simon A, Gibori H, Krayem M, Mumblat Y, Kasten S, Ofir S, Fridman E, Milman N, Lübtow MM, Liba L, Shklover J, Shainsky-Roitman J, Binenbaum Y, Hershkovitz D, Gil Z, Dvir T, Luxenhofer R, Satchi-Fainaro R, Schroeder A, 2019
Collagenase nanoparticles enhance the penetration of drugs into pancreatic tumors
ACS nano 13, 11008-11021
2.
Abumanhal-Masarweh H, da Silva D, Poley M, Zinger A, Goldman E, Krinsky N, Kleiner R, Shenbach G, Schroeder JE, Shklover J, Shainsky-Roitman J, Schroeder A, 2019
Tailoring the lipid composition of nanoparticles modulates their cellular uptake and affects the viability of triple negative breast cancer cells
J. Control. Release 307, 331-341
3.
Adir O, Poley M, Chen G, Froim S, Krinsky N, Shklover J, Shainsky-Roitman J, Lammers T, Schroeder A, 2019
Integrating Artificial Intelligence and Nanotechnology for Precision Cancer Medicine
Adv. Mater. 32, e1901989
4.
Abumanhal-Masarweh H, Koren L, Zinger A, Yaari Z, Krinsky N, Kaneti G, Dahan N, Lupu-Haber Y, Suss-Toby E, Weiss-Messer E, Schlesinger-Laufer M, Shainsky-Roitman J, Schroeder A, 2019
Sodium bicarbonate nanoparticles modulate the tumor pH and enhance the cellular uptake of doxorubicin
J. Control. Release 296, 1-13