Endometriosis is an incurable gynecological disorder characterized by abnormal growth of endometrial-like tissue outside the uterine cavity, causing pelvic pain and fertility issues in millions. Affecting about 10 % of reproductive-age women, endometriosis leads to impaired quality of life due to recurrence after existing treatments.1,2
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Nanoparticle-based therapy has gained significant attention in medicine for its potential to revolutionize traditional diagnostics and treatments. Researchers aim to improve women's lives using minimally invasive and highly effective nanotechnology-based treatments.1
This article explores emerging nanotechnology trends for endometriosis diagnosis and treatment.
Understanding Endometriosis and Current Treatment Challenges
In endometriosis, a tissue similar to the uterus’s inner lining develops outside the uterus and can extend beyond the pelvic area in rare cases.1 This unusual tissue growth transforms into cysts (endometriotic lesions) and scar tissue.2 Common symptoms include pain and infertility due to the impact on various reproductive parts.1
Accurate diagnosis of endometriosis based solely on symptoms is clinically challenging.2 Current diagnostic techniques include laparoscopy and imaging via ultrasound or magnetic resonance imaging (MRI). Laparoscopy is a surgical procedure that inflates the abdomen, while imaging methods are costly and have inadequate resolution.1
Endometriosis treatment generally involves pharmacological and surgical approaches. No existing drug can halt the disease’s progression; thus, hormones are used for temporary relief and fertility improvement.
However, hormone therapy often causes side effects like the cessation of menstruation.1 Laparoscopic surgery, on the other hand, is invasive and carries a high risk of incomplete tissue removal, leading to recurrent lesions.2
The potential of nanoparticles to dissolve insoluble drugs, prevent degradation of therapeutic agents, increase drug circulation time, target drug delivery, and reduce systemic toxicity is well established today; they are often referred to as modern “magic bullets.”
Their low toxicity, high stability, and compatibility with various biomolecules are being explored to develop new endometriosis diagnosis and treatment methods.1
Nanotechnology in Diagnosing Endometriosis
Nanotechnology can enable timely diagnosis of endometriosis and limit its progression in early stages.
Nanoparticles such as iron oxide or gold enhance the contrast of dyes used in magnetic/optical imaging. Additionally, nanoparticle-based fluorescent dyes efficiently differentiate affected tissues and cells from healthy ones.1 Fluorescence imaging using nanoparticle-based delivery systems allows targeted delivery of dyes to endometriotic lesions for efficient real-time imaging during surgeries.2
Imaging techniques like MRI and ultrasound are commonly used to diagnose endometriosis.2 Nanoparticles can improve the accuracy and sensitivity of these methods by acting as contrast agents coated with ligands designed to bind to specific reproductive tissue.1,2
This targeted method improves imaging during endometriosis diagnosis and offers a deeper understanding of the disease's origin and advancement.1
Biomarker detection is another non-invasive method to detect endometriosis.2 Endometriosis patients exhibit a distinct microbial composition in their peritoneal fluid and feces. Analyzing these microbial profiles using nanotechnology-based biosensors could aid in timely diagnosis.1
Immunosensors employing gold nanoparticles or graphene also offer easy synthesis, enhanced conductivity, and simple antibody labeling for biomolecule detection.2
Nanoparticle-based Therapeutic Approaches
Therapeutic strategies for endometriosis often use single agents targeting multiple therapeutic pathways. Nanomaterials can serve both as therapeutic agents and drug delivery systems, addressing limitations such as inadequate stability, poor bioactivity, and non-specific targeting.1
Specifically, nanoparticles can ensure targeted delivery of antioxidants or antiangiogenic compounds to prevent endometriosis progression.2
In photothermal therapy (PTT), light-sensitive nanoparticles are introduced into the patient’s body, and a near-infrared (NIR) laser is applied to the region.2 The nanoparticles convert this optical energy into heat to destroy targeted cells via protein denaturation and membrane degradation.1,2 Nanomaterials like gold nanorods and carbon nanotubes are employed to induce localized hyperthermia.1
While promising, PTT’s restricted tissue penetration of NIR light limits the treatment of deeper lesions. Magnetic hyperthermia, using magnetic fields to activate magnetic nanoparticles for heat production, offers an alternative that can effectively target innate endometriosis lesions without relying on light penetration.1,2
Nanoparticle-enhanced immunotherapy utilizes the body’s immune system to counter endometriosis lesions.1 Using nanoparticles to regulate specific immune cells (macrophages or T cells) can inhibit cells responsible for disease progression. For example, macrophages can detect and remove endometrial cells from the peritoneal cavity. However, an elevated concentration of specific macrophages promotes fibrosis and angiogenesis.2
Gene therapy involves altering genetic material for disease prevention and treatment by adding, correcting, or removing specific genes. This can be realized by delivering nucleic acids containing specific genes in the body.1
However, nucleic acids cannot be delivered alone because of their low stability and unfavorable pharmacokinetic profile. As a solution, nanocarriers such as polymeric nanoparticles, extracellular vehicles, and micelles function as reliable and efficient delivery vehicles.2
Future Outlooks
Numerous trials are being conducted to establish the efficacy of nanotechnological methods for endometriosis diagnosis and treatments. For instance, a recent study in Nanomaterials demonstrated the application of nanoparticles conjugated with cyclic arginyl-glycyl-aspartic acid (cRGD) to detect endometriosis lesions through MRI in a mouse model.
The results validated the accuracy of this nanoparticle-based probe in pointing lesions. Therefore, a proof-of-concept was established to target angiogenesis, which can assist in potential clinical diagnosis and treatments for endometriosis.3
However, mouse and rat models are inaccurate as endometriosis does not grow naturally in these animals. A primate reproductive model is more suitable for endometriosis treatment trials due to its closer similarities to the human reproductive system.2
Despite several benefits, nanoparticles accumulated in the human body can exhibit uncertain long-term impacts, necessitating thorough safety examination. A recent study in the Archives of Gynecology and Obstetrics examined the safety and feasibility of lipid nanoparticles (LDE) carrying methotrexate (MTX) to treat innate endometriosis. This test was conducted on eleven volunteers with endometriosis; none reported any clinical issues related to this treatment.
Additionally, no hematologic, renal, or hepatic toxicities were evident in the laboratory tests after 180 days of LDE-MTX administration. While the results established the safety of LDE-MTX treatment, more prolonged clinical trials should be conducted to commercialize this nanomaterial-based treatment.4
In conclusion, future efforts for endometriosis treatment should include innovations in nano-therapy design and more reliable animal models. Ensuring the safety of nanomedicines is crucial for their translatability to humans.2
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References and Further Reading
1. Talukdar, S., Singh, S. K., Mishra, MK., Singh, R. (2024). Emerging Trends in Nanotechnology for Endometriosis: Diagnosis to Therapy. Nanomaterials. doi.org/10.3390/nano14110976
2. Sahni, M., Day, ES. (2023). Nanotechnologies for the detection and treatment of endometriosis. Frontiers in Biomaterials Science. doi.org/10.3389/fbiom.2023.1279358
3. Talebloo, N., et al. (2024). Imaging of Endometriotic Lesions Using cRGD-MN Probe in a Mouse Model of Endometriosis. Nanomaterials. doi.org/10.3390/nano14030319
4. Avila-Tavares, R., et al. (2023). Pilot study of treatment of patients with deep infiltrative endometriosis with methotrexate carried in lipid nanoparticles. Archives of Gynecology and Obstetrics. doi.org/10.1007/s00404-023-07246-8
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