Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.
Department of Obstetrics and Gynecology, School of Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.
Small. 2023 Jan;19(2):e2202343. doi: 10.1002/smll.202202343. Epub 2022 Nov 17.
Ectopic pregnancy (EP) is the leading cause of maternity-related death in the first trimester of pregnancy. Approximately 98% of ectopic implantations occur in the fallopian tube, and expedient management is crucial for preventing hemorrhage and maternal death in the event of tubal rupture. Current ultrasound strategies misdiagnose EP in up to 40% of cases, and the failure rate of methotrexate treatment for confirmed EP exceeds 10%. Here the first theranostic strategy for potential management of EP is reported using a near-infrared naphthalocyanine dye encapsulated within polymeric nanoparticles. These nanoparticles preferentially accumulate in the developing murine placenta within 24 h following systemic administration, and enable visualization of implantation sites at various gestational stages via fluorescence and photoacoustic imaging. These nanoparticles do not traverse the placental barrier to the fetus or impact fetal development. However, excitation of nanoparticles localized in specific placentas with focused NIR light generates heat (>43 °C) sufficient for disruption of placental function, resulting in the demise of targeted fetuses with no effect on adjacent fetuses. This novel approach would enable diagnostic confirmation of EP when current imaging strategies are unsuccessful, and elimination of EP could subsequently be achieved using the same nano-agent to generate localized hyperthermia resulting in targeted placental impairment.
宫外孕 (EP) 是妊娠早期孕产妇死亡的主要原因。大约 98%的异位植入发生在输卵管,因此在输卵管破裂时,及时的处理对于防止出血和母亲死亡至关重要。目前的超声策略在多达 40%的病例中误诊宫外孕,并且已确诊的宫外孕患者使用甲氨蝶呤治疗的失败率超过 10%。本文报道了一种近红外萘酞菁染料包封在聚合物纳米颗粒中的用于潜在管理 EP 的首个治疗策略。这些纳米颗粒在全身给药后 24 小时内优先聚集在发育中的鼠胎盘内,并通过荧光和光声成像能够可视化不同妊娠阶段的着床部位。这些纳米颗粒不会穿过胎盘屏障进入胎儿,也不会影响胎儿发育。然而,用聚焦的近红外光激发定位于特定胎盘的纳米颗粒会产生足够的热量(>43°C),足以破坏胎盘功能,导致目标胎儿死亡,而对相邻胎儿没有影响。当目前的成像策略不成功时,这种新方法可以诊断确认 EP,随后可以使用相同的纳米剂产生局部过热,导致靶向胎盘损伤,从而消除 EP。