Anti-NRP1 peptide-engineered ROS/pH dual-responsive nanoparticles for Alpelisib delivery regulate Sema3A-NRP1/PI3K-AKT signaling to balance oxidative stress and inhibit angiogenesis in endometriosis.
Anti-NRP1 peptides just got a major spotlight in endometriosis research. A team out of Soochow University engineered nanoparticles that use an anti-NRP1 peptide coating to target problematic cells. These particles carry Alpelisib, a PI3K inhibitor, and release it only when they sense high levels of reactive oxygen species (ROS) or acidity—two hallmarks of inflamed, diseased tissue.
J Nanobiotechnology
by Zhang J, Zhang H, Liu W et al.
“Anti-NRP1 peptide-engineered ROS/pH dual-responsive nanoparticles for Alpelisib delivery regulate Sema3A-NRP1/PI3K-AKT signaling to balance oxidative stress and inhibit angiogenesis in endometriosis. Zhang J(#)(1), Zhang H(#)(1), Liu W(1), Zhang Y(1), Hou W(2), Chi C(3). Author information: (1)Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Gusu District, Suzhou, 215006, Jiangsu Province, China. (2)Gynecology and Obstetrics Department, The Fourth Affiliated Hospital of Soochow University (Dushu Lake Hospital of Suzhou), No. 9 Chongwen Road, Suzhou industrial park, Suzhou, 215000, Jiangsu Province, China. lionhoumail@hotmail.com. (3)Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Gusu District, Suzhou, 215006, Jiangsu Province, China. chichi17610@163.com. (#)Contributed equally Endometriosis progression is driven by oxidative stress and excessive angiogenesis within an inflammatory microenvironment. To overcome these challenges, we designed ROS/pH dual-responsive Alpelisib-loaded nanoparticles (Alp@TAT-AT7-NPs) functionalized with an anti-NRP1 peptide for targeted therapy. The nanoparticles exhibited superior stability, responsive drug release, and selective internalization by NRP1-overexpressing endothelial cells. In vitro results showed efficient inhibition of NRP1 and downstream PI3K/AKT signaling, along with decreased reactive oxygen species (ROS) and enhanced antioxidant enzyme activities. In an endometriosis rat model, treatment with Alp@TAT-AT7-NPs significantly reduced ectopic lesion burden and angiogenic markers (VEGF, CD34), while suppressing systemic inflammation and oxidative injury indicators such as IL-6, TNF-α, and MDA. Fluorescence imaging confirmed preferential accumulation of nanoparticles in CD31⁺ vascular regions. Mechanistic studies demonstrated that modulation of the Sema3A-NRP1-PI3K/AKT signaling axis restored redox homeostasis and inhibited pathological angiogenesis. These findings identify Alp@TAT-AT7-NPs as a synergistic nanoplatform that integrates microenvironment responsiveness with NRP1-targeted intervention, providing a promising therapeutic strategy for endometriosis. © 2026. The Author(s). Conflict of interest statement: Declarations. Ethics approval and consent to participate: All animal experiments were approved by the Animal Ethics Committee of Soochow University (No. 202508A0091). Consent for Publication: Not applicable. Competing interests: The authors declare no competing interests.”
Here’s why this matters: Endometriosis thrives on oxidative stress and abnormal blood vessel growth (angiogenesis). The researchers designed their nanoparticles to hit both problems at once. The anti-NRP1 peptide locks onto NRP1-overexpressing endothelial cells. The dual-responsive design means drug release is tightly controlled, minimizing off-target effects.
Key results from the study:
Nanoparticles showed strong stability and precise targeting of NRP1-positive cells.
In cell studies, the particles suppressed NRP1 and the downstream PI3K/AKT pathway, cutting down ROS and boosting antioxidant enzymes.
In rats, treated animals saw a big drop in lesion size, angiogenesis markers, and inflammation (lower VEGF, CD34, IL-6, TNF-α, and MDA).
Imaging confirmed the nanoparticles go right where the new blood vessels are forming.
Mechanistically, the system modulated the Sema3A-NRP1-PI3K/AKT axis. That’s a complex way of saying it restored redox balance and blocked excessive blood vessel growth—both major wins for endometriosis models.
This is a textbook example of how peptide engineering can sharpen the focus of targeted therapy. Instead of flooding the system with compounds, researchers are dialing in delivery right where it counts. Anyone following peptide research will see the significance: peptides are driving smarter, more responsive interventions for tough conditions.
Peptide-functionalized delivery systems like this aren’t just hype—they’re setting new standards for precision in disease models.
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