TY - JOUR
T1 - Nanoparticles Accumulate in the Female Reproductive System during Ovulation Affecting Cancer Treatment and Fertility
AU - Poley, Maria
AU - Mora-Raimundo, Patricia
AU - Shammai, Yael
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
N1 - Funding Information:
This work was supported by the European Union’s Horizon 2020 research and innovation program under the grant agreement no. 680242-ERC [Next-Generation Personalized Diagnostic Nanotechnologies for Predicting Response to Cancer Medicine]; a Phospholipid Research Center grant (ASC-2018-062/1-1); the Israel Science Foundation (1881/21, 1778/13, 1421/17); the Israel Ministry of Science & Technology (3-16963, 3-17418); Ministry of Agriculture & Rural Development, Office of the Chief Scientist (323/19); Israel Innovation Authority for a Nofar grant (67967, 880326), the Israel Ministry of Economy for a Kamin grant (69230, 63379); the Israel Cancer Association (2015-0116); the German-Israeli Foundation for Scientific Research and Development for a GIF Young grant (I-2328-1139.10/2012); the European Union FP-7 IRG Program for a Career Integration grant (908049); the Louis Family Cancer Research Fund, Leventhal 2020 COVID19 Research Fund (ATS #11947); a Mallat Family Foundation grant; The Unger Family Fund; and the Carrie Rosenblatt Foundation for Cancer Research. A.S. acknowledges Alon and Taub Fellowships. Images in this paper were created with BioRender.com and Adobe Illustrator. The authors also acknowledge the support of the Technion Integrated Cancer Center (TICC), the Russell Berrie Nanotechnology Institute, and the Lorry I. Lokey Interdisciplinary Center for Life Sciences & Engineering. M.P. wishes to thank the Israeli Ministry of Science and Technology for the Shulamit Aloni Doctoral Fellowship. O.A. wishes to thank the Miriam and Aaron Gutwirth Memorial Fellowship. M.K. wishes to thank TEVA Pharmaceuticals–NFBI–The National Forum for BioInnovators for a doctoral grant and the Technion Integrated Cancer Center (TICC) Rubinstein scholarship. The SPECT-CT imaging studies were funded by a CRUK Multidisciplinary Project Award [C48390/A21153], the EPSRC program for next generation molecular imaging and therapy with radionuclides [EP/S032789/1], the Wellcome EPSRC Centre for Medical Engineering at King’s College London [WT 203148/Z/16/Z], a Wellcome Trust Multiuser Equipment Grant [212885/Z/18/Z], and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and KCL [IS-BRC-1215-20006].
Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/4/26
Y1 - 2022/4/26
N2 - 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.
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.
KW - breast cancer
KW - fertility
KW - gender medicine
KW - gold nanoparticles
KW - liposome
KW - mRNA LNP
KW - ovarian cancer
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U2 - 10.1021/acsnano.1c07237
DO - 10.1021/acsnano.1c07237
M3 - Article
C2 - 35293714
AN - SCOPUS:85127311081
SN - 1936-0851
VL - 16
SP - 5246
EP - 5257
JO - ACS Nano
JF - ACS Nano
IS - 4
ER -