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

Maria Poley; Patricia Mora-Raimundo; Yael Shammai; Maya Kaduri; Lilach Koren; Omer Adir; Jeny Shklover; Janna Shainsky-Roitman; Srinivas Ramishetti; Francis Man; Rafael T.M. De Rosales; Assaf Zinger; Dan Peer; Irit Ben-Aharon; Avi Schroeder

doi:10.1021/acsnano.1c07237

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

Maria Poley, Patricia Mora-Raimundo, Yael Shammai, Maya Kaduri, Lilach Koren, Omer Adir, Jeny Shklover, Janna Shainsky-Roitman, Srinivas Ramishetti, Francis Man, Rafael T.M. De Rosales, Assaf Zinger^*, Dan Peer, Irit Ben-Aharon, Avi Schroeder^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	5246-5257
Number of pages	12
Journal	ACS Nano
Volume	16
Issue number	4
DOIs	https://doi.org/10.1021/acsnano.1c07237
State	Published - 26 Apr 2022

Funding

Funders	Funder number
Wellcome EPSRC
Mallat Family Foundation
Guy's and St Thomas' NHS Foundation Trust
Technion Integrated Cancer Center
Teva Pharmaceutical Industries
Ministry of Agriculture and Rural Development
Unger Family Fund
Carrie Rosenblatt Foundation for Cancer Research
National Institute for Health Research
NFBI
Israeli Ministry of Science and Technology for the Shulamit Aloni
Horizon 2020 Framework Programme	680242
Klinisch Chemisch Laboratorium	IS-BRC-1215-20006
Israel Science Foundation	1881/21, 1421/17, 1778/13
Israel Ministry of Economy for a Kamin	63379, 69230
Engineering and Physical Sciences Research Council	EP/S032789/1
Phospholipid Research Center	ASC-2018-062/1-1
Israel Cancer Association	2015-0116
King’s College London	WT 203148/Z/16/Z
European Union FP-7	11947, 908049
German-Israeli Foundation for Scientific Research and Development	I-2328-1139.10/2012
Cancer Research UK	C48390/A21153
Israel Innovation Authority for a Nofar	67967, 880326
Wellcome Trust	212885/Z/18/Z, 212885, 203148
Ministry of Science and Technology, Israel	3-16963, 3-17418
Chief Scientist Office, Scottish Government Health and Social Care Directorate	323/19

Keywords

breast cancer
fertility
gender medicine
gold nanoparticles
liposome
mRNA LNP
ovarian cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsnano.1c07237

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Poley, M., Mora-Raimundo, P., Shammai, Y., Kaduri, M., Koren, L., Adir, O., Shklover, J., Shainsky-Roitman, J., Ramishetti, S., Man, F., De Rosales, R. T. M., Zinger, A., Peer, D., Ben-Aharon, I., & Schroeder, A. (2022). Nanoparticles Accumulate in the Female Reproductive System during Ovulation Affecting Cancer Treatment and Fertility. ACS Nano, 16(4), 5246-5257. https://doi.org/10.1021/acsnano.1c07237

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abstract = "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.",

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author = "Maria Poley and Patricia Mora-Raimundo and Yael Shammai and Maya Kaduri and Lilach Koren and Omer Adir and Jeny Shklover and Janna Shainsky-Roitman and Srinivas Ramishetti and Francis Man and {De Rosales}, {Rafael T.M.} and Assaf Zinger and Dan Peer and Irit Ben-Aharon and Avi Schroeder",

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Poley, M, Mora-Raimundo, P, Shammai, Y, Kaduri, M, Koren, L, Adir, O, Shklover, J, Shainsky-Roitman, J, Ramishetti, S, Man, F, De Rosales, RTM, Zinger, A, Peer, D , Ben-Aharon, I & Schroeder, A 2022, 'Nanoparticles Accumulate in the Female Reproductive System during Ovulation Affecting Cancer Treatment and Fertility', ACS Nano, vol. 16, no. 4, pp. 5246-5257. https://doi.org/10.1021/acsnano.1c07237

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AU - Poley, Maria

AU - Mora-Raimundo, Patricia

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AU - Kaduri, Maya

AU - Koren, Lilach

AU - Adir, Omer

AU - Shklover, Jeny

AU - Shainsky-Roitman, Janna

AU - Ramishetti, Srinivas

AU - Man, Francis

AU - De Rosales, Rafael T.M.

AU - Zinger, Assaf

AU - Peer, Dan

AU - Ben-Aharon, Irit

AU - Schroeder, Avi

PY - 2022/4/26

Y1 - 2022/4/26

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AB - 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.

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KW - fertility

KW - gender medicine

KW - gold nanoparticles

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KW - mRNA LNP

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

Abstract

Funding

Keywords

UN SDGs

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