Specific Photothermal Ablation Therapy of Endometriosis by Targeting Delivery of Gold Nanospheres

Abstract

Endometriosis is difficult to treat since the side effects of the current therapeutic method and the high recurrence rate; thus, newer and safer therapeutic approaches are urgently needed. This work investigates the enhanced permeability and retention effect of CdTe quantum dots (QDs) and hollow gold nanospheres (HAuNS) in endometriosis to increase the delivery of HAuNS into lesion cells. The surface of HAuNS is successfully conjugated with a TNYL peptide that has specific affinity for the EphB4 receptor, which is a member of the Eph family of receptor tyrosine kinases. It is found that the EphB4 receptor is overexpressed in endometriosis lesions. The data indicate that both QDs and HAuNS can efficiently accumulate in endometriotic lesions through permeable vessels and the TNYL-conjugated HAuNS (TNYL-HAuNS) accumulate more via the interaction with EphB4. The specific photothermal ablation therapy based on TNYL-HAuNS significantly inhibits the growth of the endometriotic volume and induces the atrophy and degeneration of ectopic endometrium with no detectable toxicity to the normal organs. The level of TNF-α and estradiol also significantly decreases in the endometriotic lesions, indicating that the treatment enables a recovery from hormonal imbalance and inflammatory injury. This work can be a valuable reference for future endometriosis therapy.

Nanoparticle‐Based Platform for Activatable Fluorescence Imaging and Photothermal Ablation of Endometriosis

“…Histological assessment further confirmed penetration and accumulation of SiNc‐NP into endometriotic lesions following extravasation from the blood vessels (Figure 6D,E). As such, our results and previous reports [ 39 ] suggest that long‐circulating nanoparticles can efficiently accumulate in endometriotic lesions after systemic administration due to their extravasation through leaky vasculature, and that nanoparticle‐based systems such as the developed SiNc‐NP offer novel and less invasive opportunities for treatment and imaging of endometriosis.…”

“…[ 37 ] The similar biodistribution profiles of SiNc‐NP in mice with cancer and mice with endometriotic grafts following intravenous injection could be explained by the fact that both cancer and endometriosis are angiogenesis‐dependent diseases and the nanoparticles can accumulate in tumors and endometriotic lesions by extravasation through permeable blood vessels. [ 38,39 ] Angiogenesis represents a key factor in the growth and development of endometriotic lesions, and growing evidence in the primary literature supports a role for vascular endothelial growth factor in both the regulation of neovascularization and the increased permeability of endometriotic vascularity. [ 40 ] Immunostaining of the sectioned tissues with both Factor 8 (Figure 5D) and CD31 (Figure 6D,E) antibodies revealed the extensive vascular development in the endometriotic grafts used in our experiments that parallels angiogenesis in lesions in both macaques and women.…”

Nanomedicines for Endometriosis: Lessons Learned from Cancer Research

“…[ 49,60 ] While the use of nanoparticles in the treatment and/or imaging of endometriosis remains relatively rare, there are several reports wherein the accumulation and retention of nanoparticles in endometriotic tissues is qualitatively and/or quantitatively described. [ 11,32,33,39 ]…”

Advances in Hollow Inorganic Nanomedicines for Photothermal-Based Therapies

“…In 2017, Guo et al developed targeted HAuNS for photothermal-based endometriosis therapy. 151 Neovascularisation, a common feature of both cancer and endometriosis, is closely associated with the overexpression of Eph receptors. To achieve the targeting effect, HAuNS was conjugated with TNYL peptides, which possess remarkable binding efficiency to EphB4 receptors.…”