Personalized Cancer Treatment

Patient-specific biomarkers have helped to advance personalized medicine, however, much remains unknown when predicting whether a certain patient will or will not respond to therapy. In our lab, a nanoparticle-based technology for predicting the therapeutic potency of drugs is developed. Once a tumor is detected, a cocktail of DNA-barcoded nanoparticles, each containing a different drug, is injected intravenously. The particles accumulate in the various cells that compose the tumor microenvironment, utilizing the enhanced permeability and retention (EPR) effect.  After enabling each of the drugs to take action, a biopsy is taken from the tumor and the tissue is homogenized, to form a single-cell suspension. After sorting the cells according to cell type and to their live/dead viability state (potency screen), the DNA barcodes are extracted from the cells and the cell viability data is correlated with the type of drug/s found inside each of the cells, thereby identifying which drug or drug combination is optimal for treating the lesion. Based on the screen, a treatment protocol can be selected for the patient. Selecting a proper therapeutic that will address each patient’s unique disease presentation, can significantly improve the treatment course and outcome.

Synthetic Cells

Synthetic cells are an emerging scientific field that holds promise to transform engineered tissue into a bionic state, analogous to the technological transformation from walking or horses-and-buggies to cars and airplanes. In our research, synthetic cells are evaluated as autonomous systems for producing therapeutic proteins inside the body. Synthetic cells can exceed certain natural functions, such as producing only one protein at large amounts, or producing therapeutic proteins that are toxic to living cells. The versatile characteristics of synthetic cells will allow tailoring biologics for the personalized needs of each patient.

Targeting Tumor Microenvironment

Cancer cells need the support of other cells to progress to a tumor. Without this supporting environment, the so-called tumor microenvironment, cancer cells cannot grow. Currently, most of treatment strategies focus on killing the cancer cells. Our approach is to treat and target the supportive environment. We believe that combined targeting of the microenvironment and the tumor cells can enhance disease control and patient survival. We are designing liposomes that can carry both chemotherapeutic agents, which kill the cancer cells, and other small molecules that are aimed to attack the microenvironment. Moreover, we design liposomes that interfere with primary metabolic processes of the tumor microenvironment, including acidification, by delivering alkaline buffers to the tumor and improving chemotherapeutic agents’ activity.

Proteolytic Protein Delivery

Surgical blades are common medical tools. However, they cannot distinguish between healthy and diseased tissue, thereby creating unnecessary damage and increasing pain. We engineered nanoparticles that contain a controllable activated proteolytic enzyme. Once placed at the surgical site, the enzyme is released and activated by its co-factor, thus starting its proteolytic activity. This system was used to replace a surgery for teeth alignment, and for relaxation of the fibrotic stroma barrier that surrounds pancreatic tumors.

Targeting Metastasis

Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. Common therapeutic options become limited when dealing with metastases. In our lab, we assessed the ability of liposomal nanoparticles to target triple-negative breast cancer (TNBC) metastases in vivo. We studied the effect of several disease conditions on nanoparticle accumulation at the metastatic site, including the size of the metastases, the presence or absence of a primary tumor alongside the metastases, and the size of the metastatic lesion. Interestingly, we observed that nanoparticles may also be found in elevated levels in the pre-metastatic niche, several days before metastases are visualized by MRI or histologically in the tissue.This highlights the promise of diagnostic and therapeutic nanoparticles for treating metastatic cancer, possibly even for preventing the onset of the metastatic dissemination by targeting the pre-metastatic niche.

Agricultural Nanotechnology

There is a world-wide need for efficient agricultural technologies. The use of drug delivery systems enables treatment by overcoming biological barriers and enhancing drug targeting to diseased tissues. In our lab, we load agricultural nutrients intro nanoscale drug-delivery systems and apply them to the leaves of tomato plants. We show that liposomes are internalized by plant cell and release their encapsulated payload.  Tomato plants treated with liposomes loaded with Fe and Mg overcame acute nutrient deficiency which was not treatable using ordinary agricultural nutrients. We also interested in aquaculture and demonstrated a use of nanoparticles loaded with anti-viral RNAi in shrimp’s disease protection.

Sodium bicarbonate nanoparticles modulate the tumor pH enhancing doxorubicin uptake. Hanan Abumanhal, Assaf Zinger, Zvi Yaari, Janna Shainski Roitman and Avi Schroeder. Journal of Controlled Release, 2019, 296, 1-13. Link

Transfer of miRNA in macrophages-derived exosomes induces drug resistance of pancreatic adenocarcinoma.  Y. Binenbaum, E. Fridman, Z. Yaari, N. Milman, A. Schroeder, G. Ben David, T. Shlomi, and Ziv Gil. Cancer Research, 2018, 78(18), 5287-5299. Link

Therapeutic nanoparticles penetrate leaves and deliver nutrients to agricultural crops.  Avishai Karny, Assaf Zinger, Janna Shainsky-Roitman and Avi Schroeder. Scientific Reports, 2018, 8 (1), 7589. Link

Proteolytic Nanoparticles Replace a Surgical Blade by Controllably Remodeling the Oral Connective Tissue. Assaf Zinger, Omer Adir, Matan Alper, Chen Tzror, Assaf Simon, Maria Poley, Majd Krayem, Shira Kasten, Zvi Yaari, Avishai Herman, Yael Nir, Sharon Akrish, Tidhar Klein, Janna Shainsky-Roitman, Dov Hershkovitz, and Avi Schroeder. ACS Nano, 2018, 12 (2), 1482-1490. Link

Mucoadhesive alginate pastes with embedded liposomes for local oral drug delivery. Yarden Shtenberg, Mor Goldfeder, Hodaya Prinz, Janna Shainsky, Yasmine Ghantous, Imad Abu El-Naaj, Avi Schroeder and Havazelet Bianco-Peled. International Journal of Biological Macromolecules, 2018, 111, 62-69. Link

Anti-viral RNAi nanoparticles protect shrimp against white spot disease. (Cover) Shai Ufaz, Adi Baltar, Chen Tzror, Shai Einbender, Ori Koshet, Janna Shainsky-Roitman, Zvi Yaari and Avi Schroeder. Molecular Systems Design & Engineering – Royal Society of Chemistry, 2018, 3, 38-48. Link

Synthetic cell-like particles synthesize therapeutic proteins inside tumors. (Cover) Nitzan Krinsky, Maya Kaduri, Assaf Zinger, Janna Shainsky-Roitman, Mor Goldfeder, Itai Benhar, Dov Hershkovitz and Avi Schroeder. Advanced Healthcare Materials, 2018, 7 (9), 1701163. Link

Alginate modified with maleimide-terminated PEG as drug carriers with enhanced mucoadhesion. Yarden Shtenberg, Mor Goldfeder, Avi Schroeder, Havazelet Bianco-Peled. Carbohydrate Polymers, 2017, 175, 337-346. Link

Nanoparticles target early-stage breast cancer metastasis in vivo. Evgeniya Goldman, Assaf Zinger, Dana da Silva, Zvi Yaari, Ashima Kajal, Dikla Vardi-Oknin, Mor Goldfeder, Josh E Schroeder, Janna Shainsky-Roitman, Dov Hershkovitz and Avi Schroeder. Nanotechnology, 2017, 28(43), 43LT01. Link

Autonomous bacterial nanoswimmers target cancer. Nour Zoaby, Janna Shainsky-Roitman, Samah Badarneh, Hanan Abumanhal, Alex Leshansky, Sima Yaron, Avi Schroeder. Autonomous bacterial nanoswimmers target cancer. Journal of Controlled Release, 2017, 257, 68-75. Link

Theranostic barcoded nanoparticles for personalized cancer medicine. Zvi Yaari, Dana Da Silva, Assaf Zinger, Evgeniya Goldman, Ashima Kajal, Rafi Tshuva, Efrat Barak, Nitsan Dahan, Dov Hershkovitz, Mor Goldfeder, Janna Shainsky Roitman and Avi Schroeder.  Nature Communications, 2016, 7, 13325. Link

A simple and rapid method for preparing a cell-free bacterial lysate for protein synthesis. Nitzan Krinsky, Maya Kaduri, Janna Shainsky-Roitman, Mor Goldfeder, Eran Ivanir, Itai Benhar, Yuval Shoham and Avi Schroeder. PloS one, 2016, 11 (10), e0165137. Link

Melanoma miRNA trafficking triggers tumor primary niche formation. Shani Dror, Laureen Sander, Hila Schwartz, Danna Sheinboim, Aviv Barzilai, Yuval Dishon, Sebastien Apcher, Tamar Golan, Shoshana Greenberger, Iris Barshack, Hagar Malcov, Alona Zilberberg, Lotan Levin, Michelle Nessling, Yael Friedmann, Vivien Igras, Ohad Barzilay, Hananya Vaknine, Ronen Brenner, Assaf Zinger, Avi Schroeder, Pinchas Gonen, Mehdi Khaled, Neta Erez, Jörg D Hoheisel, Carmit Levy. Nature Cell Biology, 2016, 18, 1006–1017. Link

Ultrasound mediated gastrointestinal drug delivery. Carl M Schoellhammer, Avi Schroeder, Ruby Maa, Gregory Yves Lauwers, Albert Swiston, Michael Zervas, Ross Barman, Angela M DiCiccio, William R Brugge, Daniel G Anderson, Daniel Blankschtein, Robert Langer, Giovanni Traverso. Science Translational Medicine, 2015, 7(310), 168-172. Link

Microneedles for Drug Delivery via the Gastrointestinal Tract. Giovanni Traverso,* Carl M Schoellhammer,* Avi Schroeder,* (*equal contribution), Ruby Maa, Gregory Y Lauwers, Baris E Polat, Daniel G Anderson, Daniel Blankschtein, Robert Langer. Journal of Pharmaceutical Sciences, 2015, 104(2), 362-367. Link

Small RNA combination therapy for lung cancer. Wen Xue, James E Dahlman, Tuomas Tammela, Omar F Khan, Sabina Sood, Apeksha Dave, Wenxin Cai, Leilani M Chirino, Gillian R Yang, Roderick Bronson, Denise G Crowley, Gaurav Sahay, Avi Schroeder, Robert Langer, Daniel G Anderson, Tyler Jacks. PNAS Proceedings of the National Academy of Sciences, 2014, 111(34), E3553-E3561. Link

In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight.  James E Dahlman, Carmen Barnes, Omar F Khan, Aude Thiriot, Siddharth Jhunjunwala, Taylor E Shaw, Yiping Xing, Hendrik B Sager, Gaurav Sahay, Lauren Speciner, Andrew Bader, Roman L Bogorad, Hao Yin, Tim Racie, Yizhou Dong, Shan Jiang, Danielle Seedorf, Apeksha Dave, Kamaljeet Singh Sandhu, Matthew J Webber, Tatiana Novobrantseva, Vera M Ruda, Abigail KR Lytton-Jean, Christopher G Levins, Brian Kalish, Dayna K Mudge, Mario Perez, Ludmila Abezgauz, Partha Dutta, Lynelle Smith, Klaus Charisse, Mark W Kieran, Kevin Fitzgerald, Matthias Nahrendorf, Dganit Danino, Rubin M Tuder, Ulrich H Von Andrian, Akin Akinc, Dipak Panigrahy, Avi Schroeder, Victor Koteliansky, Robert Langer, Daniel G Anderson. Nature Nanotechnology, 2014, 9, 648-655. Link

Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates.  Yizhou Dong, Yizhou Dong, Kevin T Love, J Robert Dorkin, Sasilada Sirirungruang, Yunlong Zhang, Delai Chen, Roman L Bogorad, Hao Yin, Yi Chen, Arturo J Vegas, Christopher A Alabi, Gaurav Sahay, Karsten T Olejnik, Weiheng Wang, Avi Schroeder, Abigail KR Lytton-Jean, Daniel J Siegwart, Akin Akinc, Carmen Barnes, Scott A Barros, Mary Carioto, Kevin Fitzgerald, Julia Hettinger, Varun Kumar, Tatiana I Novobrantseva, June Qin, William Querbes, Victor Koteliansky, Robert Langer, Daniel G Anderson.  PNAS Proceedings of the National Academy of Sciences, 2013, 111(11), 3955-3960. Link

Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Gaurav Sahay, William Querbes, Christopher Alabi, Ahmed Eltoukhy, Sara Sarkar, Christopher Zurenko, Emanoel Karagiannis, Kevin Love, Delay Chen, Roy Zoncu, Yosi Buganim, Avi Schroeder, Robert Langer, Daniel G Anderson. Nature Biotechnology, 2013, 21(7), 653-658. Link

Injection of vascular endothelial growth factor into knee joints induces osteoarthritis in mice.  Aya Ludin, Jona J Sela, Avi Schroeder, Yuval Samuni, Dorrit Nitzan, Amir Gail.  Osteoarthritis Cartilage, 2013, 21(3), 491-497. Link

Modular ‘click-in-emulsion’ bone-targeted nanogels. Daniel A. Heller, Yair Levi, Jeisa M. Pelet, Joshua C. Doloff, Jasmine Wallas, George W. Pratt , Shan Jiang, Gaurav Sahay, Avi Schroeder, Josh E. Schroeder, Yieu Chyan, Christopher Zurenko, William Querbes, Miguel Manzano, Daniel S. Kohane, Robert Langer, Daniel G. Anderson.  Advanced Materials, 2013, 25(10), 1449-1454. Link

Remotely-activated protein-producing nanoparticles. Avi Schroeder, Michael S. Goldberg, Christian Kastrup, Christopher G. Levins, Robert Langer and Daniel G. Anderson. Nano Letters, 2012, 12(6), 2685–2689. Highlighted in: Nature, 2012, 484, 290. Link

Focused Ultrasound-A Novel Tool for Liposome Formulation. Srikanth Kakumanu and Avi Schroeder. Drug Development and Delivery, 2012, 12, 5, 47-52. Link

Alkane-modified short polyethyleneimine for siRNA delivery. Avi Schroeder, James Dahlman, Gaurav Sahay, Kevin T. Love, Yingxia Wang and Daniel G. Anderson. Journal of Controlled Release, 2012, 160(2), 172–176. Link

Nanoparticles for targeting the infarcted heart. Tal Dvir, Michael Bauer, Avi Schroeder, Jonathan Tsui, Daniel G. Anderson, Robert Langer, Ronglih Liao, and Daniel S. Kohane. Nano Letters, 2011, 11(10), 4411–4414. Link

Liposomes for HIV prophylaxis. Nikita Malavia, David Zurakowski, Avi Schroeder, Anna Laury, Hila Epstein-Barash, Joseph Sodroski, Robert Langer, Navid Madani, and Daniel S. Kohane.  Biomaterials, 2011, 32(33):8663-8. Link

Boundary lubricants with exceptionally-low friction coefficients based on 2-D close-packed phosphatidylcholine liposomes.  Ronit Golberg, Avi Schroeder, Keren Torgeman, Yechezkel Barenholz, Jacob Klein.  Advanced Materials, 2011, 23(31):3517-21. Link

Interactions between adsorbed unilamellar HSPC vesicles on mica surfaces across conditions of physiological osmolarity. Ronit Goldberg, Avi Schroeder, Yechezkel Barenholz, Jacob Klein.  Biophysical Journal, 2011, 100(10) 2403-2411. Link

Polyhydroxylated fatty alcohols derived from avocado suppress inflammatory response and provide non-sunscreen protection against UV-induced damage in skin cells. Gennady Rosenblat, Shai Meretski, Joseph Segal, Mark Tarshih, Avi Schroeder, Alexandra Zanin, Malka Hochberg. Archives of Dermatological Research, 2011, 303(4) 239-46. Link

Liposomes as potential biolubricant additives for wear reduction in human synovial joints. Gabi Verberne, Avi Schroeder, Grigory Halprin, Yechezkel Barenholz, Izhak Etsion.   Wear, 2010, 268 (7-8) 1037-1042. Link

Liposomes act as effective biolubricants for friction reduction in human synovial joints.  Sarit Sivan* and Avi Schroeder* (*Equal contribution), Gabi Verberne, Yulia Merkher, Dvora Diminsky, Aba Priev, Alice Maroudas, Gregory Halperin, Dorrit Nitzan, Izhak Etsion, Yechezkel Barenholz.  Langmuir, 2010, 26 (2), 1107–1116. Link

A mathematical model of drug release from liposomes by low frequency ultrasound  Giora Enden, Avi Schroeder. Annals Biomedical Engineering, 2009, 37 (12), 2640-2645. Link

Ultrasound triggered release of cisplatin from liposomes in murine tumors. Avi Schroeder, Reuma Honen, Keren Turjeman, Alberto Gabizon, Joseph Kost and Yechezkel Barenholz. Journal of Controlled Release, 2009, 137 (1), 63-68. Link

Using PEGylated nano-liposomes to target tissue invaded by a foreign body. Avi Schroeder, Alex Sigal, Keren Turjeman and Yechezkel Barenholz. Journal of Drug Targeting, 2008, 16 (7-8), 591-595. Link

Surface active phospholipids as cartilage lubricants. Avi Schroeder, Gabi Verberne, Yulia Merkher, Dvora Diminsky, Alice Maroudas, Gregory Halperin, Alexandra Barbur, Dorrit Nitzan, Izhak Etsion, Yechezkel Barenholz, Sarit Sivan. Proc. ASME ESDA, 2008, 3, 549-553. Link

Triggered release of aqueous content from liposome-derived sol-gel nano-capsules. Yael Steinberg, Avi Schroeder, Yeshayahu Talmon, Judith Schmidt, Rafail L. Khalfin, Yachin Cohen, Jean-Marie Devoisselle, Sylvie Begu, and David Avnir. Langmuir, 2007, 23 (24), 12024-12031. Link

Controlling liposomal drug release by low-frequency ultrasound: Mechanism and feasibility. Avi Schroeder, Yuval Avnir, Sara Weisman, Yousef Najajreh, Alberto Gabizon, Yeshayahu Talmon, Joseph Kost, and Yechezkel Barenholz. Langmuir, 2007, 23 (7), 4019-4025. Link