Journal
THERIOGENOLOGY
Volume 192, Issue -, Pages 132-140Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.theriogenology.2022.08.032
Keywords
Liposome vesicles; Molecular imaging; Nanoparticles; Intracellular drug delivery; Ovarian follicle injection
Categories
Funding
- National Institute of Food and Agriculture, U.S. Department of Agriculture [1016077, W4171]
- Southeast Conference (SEC) Faculty travel Grant, Office of Research and Economic Development, Mississippi State University
- USDA-ARS Biophotonics [6066-31000-015-00D]
- Southern Illinois University
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Despite advancements in assisted reproductive techniques, there is still a need for rapid and minimally invasive in situ approaches to enhance female fertility. Researchers synthesized clinically relevant liposome nanoparticles and injected them into ovarian follicles of mares, achieving successful intrafollicular binding and migration of liposomes between different cell layers. Furthermore, the potential for intracellular delivery of nanoparticles was confirmed in porcine follicle wall cell types.
Despite the progress in assisted reproductive techniques, there is still a lack of rapid and minimally invasive in situ approaches for further enhancements of female fertility. Therefore, we synthesized clinically relevant liposome nanoparticles for ovarian intrafollicular injection to allow in vivo cellular imaging for future drug delivery, using the mare as an animal model. Ovarian follicles of living mares were injected in vivo with fluorescently labeled liposomes. Samples of the follicular wall (mural granulosa, theca interna, and theca externa), granulosa cells, and follicular fluid were harvested 24 h postinjection through the follicle wall biopsy (FWB), flushing, and aspiration techniques, respectively, using a transvaginal ultrasound-guided approach. In parallel, post-mortem dissected, and cultured porcine antral follicles were microinjected with doxorubicin-encapsulated liposomes to assess intracellular delivery potential. All injected mare and pig follicles were macroscopically healthy, and fluorescence imaging revealed successful intrafollicular binding to mural granulosa cells and progressive migration of liposomes to other follicle cell layers (theca interna, and theca externa), regardless of the follicle size. Intracellular delivery of doxorubicin was confirmed in all porcine follicle wall cell types. We conclude that the intrafollicular injection of nanomolecules is a promising approach for real-time monitoring of intrafollicular processes and potential utilization of in vivo cellular drug delivery to assist in follicle disease treatments and fertility improvement. (c) 2022 Elsevier Inc. All rights reserved.
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