Maria Poley

University of California, San Francisco

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Avi Schroeder

Technion – Israel Institute of Technology

Janna Shainsky‐Roitman

Technion – Israel Institute of Technology

Jeny Shklover

Technion – Israel Institute of Technology

Omer Adir

Technion – Israel Institute of Technology

Maya Kaduri

Technion – Israel Institute of Technology

Gal Chen

Technion – Israel Institute of Technology

Nitzan Krinsky

Technion – Israel Institute of Technology

Dov Hershkovitz

Tel Aviv Sourasky Medical Center

Lilach Koren

Novocure (United States)

Patricia Mora‐Raimundo

Technion – Israel Institute of Technology

Cooperative Institutions

Technion – Israel Institute of Technology

Tel Aviv University

Hebrew University of Jerusalem

Rappaport Family Institute for Research in the Medical Sciences

University of Haifa

Rambam Health Care Campus

Harvard University

Weizmann Institute of Science

Bar-Ilan University

Hadassah Medical Center

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Sex‐Based Differences in the Biodistribution of Nanoparticles and Their Effect on Hormonal, Immune, and Metabolic Function

Advanced NanoBiomed Research (2022)

Maria Poley Gal Chen Noga Sharf-Pauker Aviram Avital Maya Kaduri

Males and females respond differently to medications due to physiologic, metabolic, and genetic factors. At times, sex‐related differences cannot be mitigated by dose adjustment to body mass, and are evident from the tissue level to the single cell. The rising number of clinically approved nanotechnologies calls for assessing how their activity is affected by the patient's sex. Herein, sex differences in nanotechnology are scoped, with emphasis on molecular considerations. Sex‐specific pharmacokinetics of nanocarriers is influenced by the nanoparticle's composition, its size, and architecture. The biodistribution and immune response to nanoparticles in males and females, and the influence nanoparticles have on hormones, fertility, and toxicity, are discussed. Despite its importance, the effect of sex on the design and implementation of nanomedicines is underresearched. Herein, it is aimed to raise awareness of sex differences in the preclinical and clinical evaluation of nanotechnologies.

Nanocarriers

Biodistribution

10.1002/anbr.202200089

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Citations (15)

Integrating Artificial Intelligence and Nanotechnology for Precision Cancer Medicine

Advanced Materials (2019)

Omer Adir Maria Poley Gal Chen Sahar Froim Nitzan Krinsky

Abstract Artificial intelligence (AI) and nanotechnology are two fields that are instrumental in realizing the goal of precision medicine—tailoring the best treatment for each cancer patient. Recent conversion between these two fields is enabling better patient data acquisition and improved design of nanomaterials for precision cancer medicine. Diagnostic nanomaterials are used to assemble a patient‐specific disease profile, which is then leveraged, through a set of therapeutic nanotechnologies, to improve the treatment outcome. However, high intratumor and interpatient heterogeneities make the rational design of diagnostic and therapeutic platforms, and analysis of their output, extremely difficult. Integration of AI approaches can bridge this gap, using pattern analysis and classification algorithms for improved diagnostic and therapeutic accuracy. Nanomedicine design also benefits from the application of AI, by optimizing material properties according to predicted interactions with the target drug, biological fluids, immune system, vasculature, and cell membranes, all affecting therapeutic efficacy. Here, fundamental concepts in AI are described and the contributions and promise of nanotechnology coupled with AI to the future of precision cancer medicine are reviewed.

Cancer Therapy

10.1002/adma.201901989

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Citations (323)

Tailoring the lipid composition of nanoparticles modulates their cellular uptake and affects the viability of triple negative breast cancer cells

Journal of Controlled Release (2019)

Hanan Abumanhal-Masarweh Dana da Silva Maria Poley Assaf Zinger Evgenya Goldman

Viability assay

Cell membrane

Triple-negative breast cancer

10.1016/j.jconrel.2019.06.025

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Citations (74)

Brain‐Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha‐Synuclein Aggregation and Improve Behavioral Symptoms in Parkinson's Disease (Adv. Mater. 51/2023)

Advanced Materials (2023)

Mor Sela Maria Poley Patricia Mora‐Raimundo Shaked Kagan Aviram Avital

Brain-Targeted Liposomes In article number 2304654, Avi Schroeder and co-workers describe a targeted nanotechnology drug delivery system for treating Parkinson's disease. Brain-targeted liposomes—nanoparticles engineered with transferrin on their surface and carry therapeutic antibodies, cross the blood–brain barrier and effectively treat brain neurodegeneration. This approach reduces pathological alpha-synuclein aggregation and improves motor skills, demonstrating its potential for treating neurodegenerative diseases.

Targeted drug delivery

10.1002/adma.202370367

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Barriers in the Tumor Microenvironment to Nanoparticle Activity

Hanan Abumanhal-Masarweh Lilach Koren Omer Adir Maya Kaduri Maria Poley

This chapter explores tumoral barriers for the successful implementation of nanomedicines. Nanotechnologies hold great clinical promise to improve the efficacy of diagnostic and therapeutic anticancer agents. In cancer therapy, many nanotechnologies target solid tumors through the leaky tumor vasculature and/or using surface ligands with molecular specificity to biomarkers in the tumor tissue. Traditional approaches of loading nanoparticles solely with drugs aimed at killing the cancer cells are being replaced by multiple agents for targeting the various components of the tumor microenvironment. The demand for nutrients and oxygen by a developing tumor is accommodated by angiogenesis— the formation of new blood vessels. The extracellular matrix (ECM) is a woven net between tissues and organs composed of water, minerals, proteins, proteoglycans and glycoproteins such as collagen, fibronectin, hyaluronic acid, and many others. The dynamic nature of the ECM is particularly apparent during development, wound healing, cancer and other diseases.

10.1201/9781003125259-15

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Brain‐Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha‐Synuclein Aggregation and Improve Behavioral Symptoms in Parkinson's Disease

Advanced Materials (2023)

Mor Sela Maria Poley Patricia Mora‐Raimundo Shaked Kagan Aviram Avital

Abstract Monoclonal antibodies (mAbs) hold promise in treating Parkinson's disease (PD), although poor delivery to the brain hinders their therapeutic application. In the current study, it is demonstrated that brain‐targeted liposomes (BTL) enhance the delivery of mAbs across the blood‐brain‐barrier (BBB) and into neurons, thereby allowing the intracellular and extracellular treatment of the PD brain. BTL are decorated with transferrin to improve brain targeting through overexpressed transferrin‐receptors on the BBB during PD. BTL are loaded with SynO4, a mAb that inhibits alpha‐synuclein (AS) aggregation, a pathological hallmark of PD. It is shown that 100‐nm BTL cross human BBB models intact and are taken up by primary neurons. Within neurons, SynO4 is released from the nanoparticles and bound to its target, thereby reducing AS aggregation, and enhancing neuronal viability. In vivo, intravenous BTL administration results in a sevenfold increase in mAbs in brain cells, decreasing AS aggregation and neuroinflammation. Treatment with BTL also improve behavioral motor function and learning ability in mice, with a favorable safety profile. Accordingly, targeted nanotechnologies offer a valuable platform for drug delivery to treat brain neurodegeneration.

Transferrin receptor

10.1002/adma.202304654

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Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Maya Kaduri Mor Sela Shaked Kagan Maria Poley Hanan Abumanhal-Masarweh

Abstract Neurons within the tumor microenvironment promote cancer progression, thus their local targeting has potential clinical benefits. We designed PEGylated lipid nanoparticles loaded with a non-opioid analgesic, bupivacaine, to target neurons within breast cancer tumors and suppress nerve-to-cancer crosstalk. In vitro , 100-nm nanoparticles were taken up readily by primary neurons, trafficking from the neuronal body and along the axons. We demonstrate that signaling between triple-negative breast cancer cells (4T1) and neurons involves secretion of cytokines stimulating neurite outgrowth. Reciprocally, neurons stimulated 4T1 proliferation, migration and survival through secretion of neurotransmitters. Bupivacaine curbs neurite growth and signaling with cancer cells, inhibiting cancer-cell viability. In vivo , bupivacaine-loaded nanoparticles administered intravenously, suppressed neurons in orthotopic triple-negative breast cancer tumors, inhibiting tumor growth and metastatic dissemination. Overall, our findings suggest that reducing nerve involvement in tumors is important for treating cancer.

Neurite

Crosstalk

10.1101/2021.05.18.444598

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Nanoparticles Accumulate in the Female Reproductive System during Ovulation Affecting Cancer Treatment and Fertility

ACS Nano (2022)

Maria Poley Patricia Mora‐Raimundo Yael Shammai Maya Kaduri Lilach Koren

Throughout the female menstrual cycle, physiological changes occur that affect the biodistribution of nanoparticles within the reproductive system. We demonstrate a 2-fold increase in nanoparticle accumulation in murine ovaries and uterus during ovulation, compared to the nonovulatory stage, following intravenous administration. This biodistribution pattern had positive or negative effects when drug-loaded nanoparticles, sized 100 nm or smaller, were used to treat different cancers. For example, treating ovarian cancer with nanomedicines during mouse ovulation resulted in higher drug accumulation in the ovaries, improving therapeutic efficacy. Conversely, treating breast cancer during ovulation, led to reduced therapeutic efficacy, due to enhanced nanoparticle accumulation in the reproductive system rather than at the tumor site. Moreover, chemotherapeutic nanoparticles administered during ovulation increased ovarian toxicity and decreased fertility compared to the free drug. The menstrual cycle should be accounted for when designing and implementing nanomedicines for females.

Biodistribution

10.1021/acsnano.1c07237

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Citations (22)

Proteolytic Nanoparticles Replace a Surgical Blade by Controllably Remodeling the Oral Connective Tissue

ACS Nano (2018)

Assaf Zinger Omer Adir Matan Alper Assaf Simon Maria Poley

Surgical blades are common medical tools. However, blades cannot distinguish between healthy and diseased tissue, thereby creating unnecessary damage, lengthening recovery, and increasing pain. We propose that surgical procedures can rely on natural tissue remodeling tools-enzymes, which are the same tools our body uses to repair itself. Through a combination of nanotechnology and a controllably activated proteolytic enzyme, we performed a targeted surgical task in the oral cavity. More specifically, we engineered nanoparticles that contain collagenase in a deactivated form. Once placed at the surgical site, collagenase was released at a therapeutic concentration and activated by calcium, its biological cofactor that is naturally present in the tissue. Enhanced periodontal remodeling was recorded due to enzymatic cleavage of the supracrestal collagen fibers that connect the teeth to the underlying bone. When positioned in their new orientation, natural tissue repair mechanisms supported soft and hard tissue recovery and reduced tooth relapse. Through the combination of nanotechnology and proteolytic enzymes, localized surgical procedures can now be less invasive.

Proteolytic enzymes

10.1021/acsnano.7b07983

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Citations (22)

Sex-Specific Considerations in Nanomedicine: Highlighting the Impact of the Menstrual Cycle on Drug Development

Nanomedicine (2023)

Maria Poley

Tweetable abstract The female menstrual cycle is one of the most overlooked sex-specific factors in drug distribution and response. Unlocking the potential of nanomedicine demands a fundamental understanding of the impact biological sex has on drug distribution, efficacy and adverse effects.

10.2217/nnm-2023-0347

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