Yuichiro Miyake, MD - Best of the Best in Pediatric Surgery 2024

OK, so we go on to the 3rd presentation of this 2nd slot is Doctor Shuishhiro Miyake representing CAPS with the work using microinjection for drug delivery with nanoparticles in lung explants to study prenatal treatment of congenital diaphragmatic hernia. So, let's see it. Thank you very much for the opportunity to present today. Can you imagine a future where congenital anomalies can be treated during fetal development with nanoparticles? Today, I'm going to talk about using microinjection technique with nanoparticles to study prenatal treatment of congenital diaphragmatic hernia. We have no COI to disclose. Congenital diaphragmatic hernia patient present with a hole in the diaphragm, and abnormal lung development resulting in lung hyperpressure and persistent pulmonary hypertension. The incidence of CDH is 1 in 2000 to 5000 live births, and about 150 CDH babies are born every day in the world. However, the survival rate of CDH is low, and about 50 CDH babies die every day. Currently, phytoscopic endoluminal tracheal occlusion is performed to increase survival rate of CDH babies. In a randomized controlled trial, it was reported fatal improved the survival rate for severe CDH from 15% to 40%. However, the mortality of CDH remains high, and we have to achieve further improved outcomes. So what can we do to improve the outcome of sedate babies? This should be a challenge for all pediatric surgeons. To address this challenge, our approach involves using nanoparticles. The chitosone nanoparticles possess the ability to encapsulate various therapeutic substances. We hypothesize combining fetal with nanoparticles-based drug delivery could potentially lead to even better outcomes for CH babies. In the past year, we established the fetal model in rat lung explant and we started to study nanoparticles injection into the trachea during fetal for drug delivery. In this study, we created a specially designed microinjector based on a microinsemination device. This allowed us to investigate the combination of fetal with drug administration. Rat fetuses were removed on embryonic day 18. After dissecting the lungs, we injected nanoparticles into the trachea. Then the trachea was tied with a surgical suture to replicate the fetal model. A variation parameters are as follows. An IgG antibody selected to target pulmonary tissue was used to functionalize the nanoparticles. We also checked apoptosis and inflammation markers to investigate potential adverse effect of nanoparticles. We performed immunofluorescence to investigate the distribution of nanoparticles. As you can see, IgG nanoparticles exhibited superior uptake into the lungs compared to bare nanoparticles. In fact, the relative number of nanoparticles to DI was about 2.5-fold higher in the IgG nanoparticles group. However, the active caspase 3 protein abundance and IL-6 protein abundance were not significantly different among the control B nanoparticles and IgG nanoparticles group. Our microinjection model in lung explant confirmed the uptake of nanoparticles in the fetal lung tissues. IgG nanoparticles was better taken up into the lungs without obvious side effect. Our research represent a significant step forward in the quest to improve outcomes for CDH babies. This model offers a controlled platform to investigate the potential of prenatal therapy with nanoparticles. We believe further studies with therapeutic agent can reveal better prenatal therapies in CDH lungs. And save the cityage babies. Thank you very much for your attention. Awesome. Um, thank you, Doctor Miyake, for this presentation. Um, I really enjoy it. So I have one question. So this immunoglobulins that you inject into the mice were taken from the fetus itself or were taken from the mom where it was gesting? Thank you very much for your question. We dissect the mother and taken the lungs from the pups of 8. And we inject the nanoparticle into the lungs and tie the trachea and culture them for, for 2 or 3 days and check them uh where nanoparticle went. OK, so to move this into a more like clinical practice into like, um. Our actual babies, we will need to make 2 injections in the uterus. Thank you very much. Uh, that's a very good point because we are considering, uh, we are, we hope we can adapt this technique to prenatal therapy in human, and, but there are many challenges that must be overcome. So we have some candidate of therapeutic agent. So we, next, for next step, we Uh, trying to encapsulate the therapeutic agent in this chitosone nanoparticles and inject the, to the lung explant. Whether they could improve the language development or not. After that, yeah, we can check them to. Yeah, in the model. Awesome. Great. OK, so I think, um, thank you very much for your time. Um, phenomenal work, yeah, thank you very much.