Application of nanoparticles in the therapeutic management of endometrial cancer

The management of endometrial cancer (EC) remains challenging due to metastatic risk, therapeutic resistance, and the modest durability of standard regimens. Nanotechnology offers a promising avenue to overcome these limitations by enhancing tumor-selective drug delivery, enabling controlled release, and facilitating multimodal approaches that integrate therapy and imaging. This review systematically summarizes recent advances in nanoparticle applications for EC, focusing on strategies that target key molecular drivers, such as TP53, PI3K/PTEN, and immune checkpoints, and evaluates localized administration routes such as vaginal delivery. Preclinical studies, including the demonstration of JX06-loaded nanoparticles combined with metformin achieving approximately 86% viability inhibition in patient-derived EC cells, underscore the potential of nanoformulations to improve intracellular delivery and therapeutic efficacy. However, current research remains constrained by its reliance on limited cell lines and immunodeficient animal models. Clinically validated active targeting efficacy has yet to be established in EC, and translational progress is further hindered by the inconsistent enhanced permeability and retention (EPR) effect, accelerated blood clearance upon repeated dosing, as well as manufacturing and regulatory challenges. Through rational design of the targeting functionality and controlled-release properties of nanocarriers, combined with EC-specific disease models and biomarker-guided clinical trials, nanotechnology holds promise for overcoming existing therapeutic limitations. With continued advancement in translational research, nanotherapeutic platforms are expected to synergize with surgery, radiotherapy, and systemic treatments, thereby paving the way for more durable and personalized therapeutic options for EC patients. This review systematically summarizes the latest research progress in nanotechnology for EC treatment, providing a solid theoretical foundation and clear research directions to accelerate the clinical translation of nanomedicine in this field.