Natasha Pritchard1,2, Tu'uhevaha Kaitu'u-Lino1,2,3, Lynda Harris4,5,6, Stephen Tong1,2, Natalie Hannan1,2,7. 1. Translational Obstetrics Group, Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia. 2. Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia. 3. Department of Obstetrics and Gynaecology, Diagnostics Discovery and Reverse Translation, University of Melbourne, Heidelberg, Victoria, Australia. 4. Division of Pharmacy and Optometry, University of Manchester, Manchester, UK. 5. Maternal and Fetal Health Research Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. 6. Maternal and Fetal Health Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester, UK. 7. Therapeutics Discovery and Vascular Function Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, Victoria, Australia.
Abstract
BACKGROUND: Nanotechnology involves the engineering of structures on a molecular level. Nanomedicine and nano-delivery systems have been designed to deliver therapeutic agents to a target site or organ in a controlled manner, maximizing efficacy while minimizing off-target effects of the therapeutic agent administered. In both reproductive medicine and obstetrics, developing innovative therapeutics is often tempered by fears of damage to the gamete, embryo or developing foetus or of negatively impacting a woman's reproductive potential. Thus, nanomedicine delivery systems may provide alternative targeted intervention strategies, treating the source of the disease and minimizing long-term consequences for the mother and/or her foetus. OBJECTIVE AND RATIONALE: This review summarizes the current state of nanomedicine technology in reproductive medicine and obstetrics, including safety, potential applications, future directions and the hurdles for translation. SEARCH METHODS: A comprehensive electronic literature search of PubMed and Web of Science databases was performed to identify studies published in English up until February 2020. Relevant keywords were used to obtain information regarding use of nanoparticle technology in fertility and gene therapy, early pregnancy complications (ectopic pregnancy and gestational trophoblastic disease) and obstetric complications (preeclampsia, foetal growth restriction, preterm birth and gestational diabetes) and for selective treatment of the mother or foetus. Safety of specific nanoparticles to the gamete, embryo and foetus was also investigated. OUTCOMES: Pre-clinical research in the development of nanoparticle therapeutic delivery is being undertaken in many fields of reproductive medicine. Non-hormonal-targeted nanoparticle therapy for fibroids and endometriosis may provide fertility-sparing medical management. Delivery of interventions via nanotechnology provides opportunities for gene manipulation and delivery in mammalian gametes. Targeting cytotoxic treatments to early pregnancy tissue provides an alternative approach to manage ectopic pregnancies and gestational trophoblastic disease. In pregnancy, nanotherapeutic delivery offers options to stably deliver silencing RNA and microRNA inhibitors to the placenta to regulate gene expression, opening doors to novel genetic treatments for preeclampsia and foetal growth restriction. Restricting delivery of teratogenic drugs to the maternal compartment (such as warfarin) may reduce risks to the foetus. Alternatively, targeted delivery of drugs to the foetus (such as those to treat foetal arrythmias) may minimize side effects for the mother. WIDER IMPLICATIONS: We expect that further development of targeted therapies using nanoparticles in a reproductive setting has promise to eventually allow safe and directed treatments for conditions impacting the health and reproductive capacity of women and for the management of pregnancy and serious pregnancy complications.
BACKGROUND: Nanotechnology involves the engineering of structures on a molecular level. Nanomedicine and nano-delivery systems have been designed to deliver therapeutic agents to a target site or organ in a controlled manner, maximizing efficacy while minimizing off-target effects of the therapeutic agent administered. In both reproductive medicine and obstetrics, developing innovative therapeutics is often tempered by fears of damage to the gamete, embryo or developing foetus or of negatively impacting a woman's reproductive potential. Thus, nanomedicine delivery systems may provide alternative targeted intervention strategies, treating the source of the disease and minimizing long-term consequences for the mother and/or her foetus. OBJECTIVE AND RATIONALE: This review summarizes the current state of nanomedicine technology in reproductive medicine and obstetrics, including safety, potential applications, future directions and the hurdles for translation. SEARCH METHODS: A comprehensive electronic literature search of PubMed and Web of Science databases was performed to identify studies published in English up until February 2020. Relevant keywords were used to obtain information regarding use of nanoparticle technology in fertility and gene therapy, early pregnancy complications (ectopic pregnancy and gestational trophoblastic disease) and obstetric complications (preeclampsia, foetal growth restriction, preterm birth and gestational diabetes) and for selective treatment of the mother or foetus. Safety of specific nanoparticles to the gamete, embryo and foetus was also investigated. OUTCOMES: Pre-clinical research in the development of nanoparticle therapeutic delivery is being undertaken in many fields of reproductive medicine. Non-hormonal-targeted nanoparticle therapy for fibroids and endometriosis may provide fertility-sparing medical management. Delivery of interventions via nanotechnology provides opportunities for gene manipulation and delivery in mammalian gametes. Targeting cytotoxic treatments to early pregnancy tissue provides an alternative approach to manage ectopic pregnancies and gestational trophoblastic disease. In pregnancy, nanotherapeutic delivery offers options to stably deliver silencing RNA and microRNA inhibitors to the placenta to regulate gene expression, opening doors to novel genetic treatments for preeclampsia and foetal growth restriction. Restricting delivery of teratogenic drugs to the maternal compartment (such as warfarin) may reduce risks to the foetus. Alternatively, targeted delivery of drugs to the foetus (such as those to treat foetal arrythmias) may minimize side effects for the mother. WIDER IMPLICATIONS: We expect that further development of targeted therapies using nanoparticles in a reproductive setting has promise to eventually allow safe and directed treatments for conditions impacting the health and reproductive capacity of women and for the management of pregnancy and serious pregnancy complications.
Authors: J M Meerum Terwogt; W W ten Bokkel Huinink; J H Schellens; M Schot; I A Mandjes; M G Zurlo; M Rocchetti; H Rosing; F J Koopman; J H Beijnen Journal: Anticancer Drugs Date: 2001-04 Impact factor: 2.248
Authors: Simon J Hawkins; Lucy A Crompton; Aman Sood; Margaret Saunders; Noreen T Boyle; Amy Buckley; Aedín M Minogue; Sarah F McComish; Natalia Jiménez-Moreno; Oscar Cordero-Llana; Petros Stathakos; Catherine E Gilmore; Stephen Kelly; Jon D Lane; C Patrick Case; Maeve A Caldwell Journal: Nat Nanotechnol Date: 2018-04-02 Impact factor: 39.213
Authors: Tu'uhevaha J Kaitu'u-Lino; Scott Pattison; Louie Ye; Laura Tuohey; Pavel Sluka; Jennifer MacDiarmid; Himanshu Brahmbhatt; Terrence Johns; Andrew W Horne; Jeremy Brown; Stephen Tong Journal: Endocrinology Date: 2013-01-03 Impact factor: 4.736