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 journalArticlepeer-review

18 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 languageEnglish
Pages (from-to)5246-5257
Number of pages12
JournalACS Nano
Volume16
Issue number4
DOIs
StatePublished - 26 Apr 2022

Funding

FundersFunder number
Carrie Rosenblatt Foundation for Cancer Research
European Union FP-711947, 908049
Israel Innovation Authority for a Nofar67967, 880326
Israel Ministry of Economy for a Kamin63379, 69230
Israeli Ministry of Science and Technology for the Shulamit Aloni
Mallat Family Foundation
NFBI
Technion Integrated Cancer Center
Unger Family Fund
Wellcome EPSRC
Teva Pharmaceutical Industries
King’s College LondonWT 203148/Z/16/Z
King’s College London
Wellcome Trust212885/Z/18/Z
Wellcome Trust
Horizon 2020 Framework Programme680242
Horizon 2020 Framework Programme
Chief Scientist Office, Scottish Government Health and Social Care Directorate323/19
Chief Scientist Office, Scottish Government Health and Social Care Directorate
Engineering and Physical Sciences Research CouncilEP/S032789/1
Engineering and Physical Sciences Research Council
National Institute for Health Research
Cancer Research UKC48390/A21153
Cancer Research UK
German-Israeli Foundation for Scientific Research and DevelopmentI-2328-1139.10/2012
German-Israeli Foundation for Scientific Research and Development
Israel Cancer Association2015-0116
Israel Cancer Association
Israel Science Foundation1881/21, 1421/17, 1778/13
Israel Science Foundation
Ministry of Agriculture and Rural Development
Guy's and St Thomas' NHS Foundation Trust
Ministry of Science and Technology, Israel3-16963, 3-17418
Ministry of Science and Technology, Israel
Klinisch Chemisch LaboratoriumIS-BRC-1215-20006
Klinisch Chemisch Laboratorium
Phospholipid Research CenterASC-2018-062/1-1
Phospholipid Research Center

    Keywords

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

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