Nanomedicines for Endometriosis: Lessons Learned from Cancer Research

Moses, Abraham S.; Demessie, Ananiya A.; Taratula, Olena; Korzun, Tetiana; Slayden, Ov D.

doi:10.1002/smll.202004975

Cited by 43 publications

(58 citation statements)

References 201 publications

(307 reference statements)

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“…Endometriosis (EMs) represents a chronic, inflammatory gynecological condition characterized by the presence of the uterine lining outside the uterine cavity [ 1 ]. EMs can be anatomically divided into three sub-groups: superficial peritoneal endometriosis, deeply infiltrating endometriosis, and ovarian endometriosis (O-EMs) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis

et al. 2022

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Endometriosis (EMs) is a benign gynecological disorder showing some tumor-like migratory and invasive phenotypes. This study intended to investigate the role of microRNA-30c (miR-30c) in EMs, which is involved with B-cell lymphoma 9 (BCL9), an activator of the Wnt/β-catenin signaling pathway. EMs specimens were clinically collected for determination of miR-30c and BCL9 expression. Exosomes were isolated from endometrial epithelial cells (EECs), and the uptake of exosomes by ectopic EECs (ecto-EECs) was characterized using fluorescence staining and confocal microscopy. The binding of miR-30c to BCL9 was validated by dual-luciferase reporter assay. Artificial modulation (up- and down-regulation) of the miR-30c/BCL9/Wnt/CD44 regulatory cascade was performed to evaluate its effect on ecto-EEC invasion and migration, as detected by Transwell and wound healing assays. A mouse model of EMs was further established for in vivo substantiation. Reduced miR-30c expression and elevated BCL9 expression was revealed in EMs ectopic tissues and ecto-EECs. Normal EECs-derived exosomes delivered miR-30c to ecto-EECs to suppress their invasive and migratory potentials. Then, miR-30c was observed to inhibit biological behaviors of ecto-EECs by targeting BCL9, and the miR-30c-induced inhibitory effect was reversed by BCL9 overexpression. Further, miR-30c diminished the invasion and migration of ecto-EECs by blocking the BCL9/Wnt/CD44 axis. Moreover, miR-30c-loaded exosomes attenuated the metastasis of ecto-EEC ectopic nodules. miR-30c delivered by EECs-derived exosomes repressed BCL9 expression to block the Wnt/β-catenin signaling pathway, thus attenuating the tumor-like behaviors of ecto-EECs in EMs.

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Section: Introductionmentioning

confidence: 99%

Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis

et al. 2022

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“…One technology in its infancy for the treatment of endometriosis is the use of nanoparticles to aid in the imaging of, directly treating or delivering drugs to treat endometriosis ( 87 ). The key limitation for this emerging technology is that the etiology and pathogenesis of endometriosis are unknown ( 87 ). Despite this, investment in nanomedicines for endometriosis could substantially augment the capacity to diagnose and treat endometriosis.…”

Section: Evolving Possibilitiesmentioning

confidence: 99%

“…Despite this, investment in nanomedicines for endometriosis could substantially augment the capacity to diagnose and treat endometriosis. Nanoparticles have shown a capacity to accumulate in endometriotic lesions ( 87 ), which could improve the use of imaging technologies to diagnose endometriosis. This technology could also provide a method for targeting endometriotic lesions without the requirement of surgery.…”

Section: Evolving Possibilitiesmentioning

confidence: 99%

Endometriosis Is Undervalued: A Call to Action

Ellis

Munro

Clarke

2022

Front. Glob. Womens Health

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Endometriosis is an inflammatory chronic pain condition caused by uterine tissue growing outside of the uterus that afflicts at least 11% of women (and people assigned female at birth) worldwide. This condition results in a substantial burden to these women, and society at large. Although endometriosis was first identified over 160 years ago, substantial knowledge gaps remain, including confirmation of the disease's etiology. Research funding for endometriosis is limited, with funding from bodies like the National Institutes of Health (NIH) constituting only 0.038% of the 2022 health budget—for a condition that affects 6.5 million women in the US alone and over 190 million worldwide. A major issue is that diagnosis of endometriosis is frequently delayed because surgery is required to histologically confirm the diagnosis. This delay increases symptom intensity, the risk of central and peripheral sensitization and the costs of the disease for the patient and their nation. Current conservative treatments of presumed endometriosis are pain management and birth control. Both of these methods are flawed and can be entirely ineffective for the reduction of patient suffering or improving ability to work, and neither addresses the severe infertility issues or higher risk of certain cancers. Endometriosis research deserves the funding and attention that befits a disease with its substantial prevalence, effects, and economic costs. This funding could improve patient outcomes by introducing less invasive and more timely methods for diagnosis and treatment, including options such as novel biomarkers, nanomedicine, and microbiome alterations.

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“…Several studies show that nanoparticles of different core composition (Au, Cd, polymers, lipids, etc. ), size range (10-150 nm), and surface charge (+30-−20 mV) accumulate in endometriotic tissue [37]. The AgNPs that we used here share some features (size ~100 nm, surface PEGylation, and negative Z-potential) with clinically used…”

Section: Pl1-targeted Nanoparticles Internalize In 12z and Hesc Cellsmentioning

confidence: 99%

Homing Peptide-Based Targeting of Tenascin-C and Fibronectin in Endometriosis

et al. 2021

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The current diagnostic and therapeutic strategies for endometriosis are limited. Although endometriosis is a benign condition, some of its traits, such as increased cell invasion, migration, tissue inflammation, and angiogenesis are similar to cancer. Here we explored the application of homing peptides for precision delivery of diagnostic and therapeutic compounds to endometriotic lesions. First, we audited a panel of peptide phages for the binding to the cultured immortalized endometriotic epithelial 12Z and eutopic stromal HESC cell lines. The bacteriophages displaying PL1 peptide that engages with angiogenic extracellular matrix overexpressed in solid tumors showed the strongest binding to both cell lines. The receptors of PL1 peptide, tenascin C domain C (TNC-C) and fibronectin Extra Domain-B (Fn-EDB), were expressed in both cells. Silver nanoparticles functionalized with synthetic PL1 peptide showed specific internalization in 12Z and HESC cells. Treatment with PL1-nanoparticles loaded with the potent antimitotic drug monomethyl auristatin E decreased the viability of endometriotic cells in 2D and 3D cultures. Finally, PL1-nanoparticless bound to the cryosections of clinical peritoneal endometriotic lesions in the areas positive for TNC-C and Fn-EDB immunoreactivities and not to sections of normal endometrium. Our findings suggest potential applications for PL1-guided nanoparticles in precision diagnosis and therapy of endometriosis.

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Nanomedicines for Endometriosis: Lessons Learned from Cancer Research

Cited by 43 publications

References 201 publications

Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis

Endometrial epithelial cells-derived exosomes deliver microRNA-30c to block the BCL9/Wnt/CD44 signaling and inhibit cell invasion and migration in ovarian endometriosis

Endometriosis Is Undervalued: A Call to Action

Homing Peptide-Based Targeting of Tenascin-C and Fibronectin in Endometriosis

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