Engineering Hybrid Polymeric Gd ₂ O ₃ Nanoparticles for Tumor‐Targeted Neutron Capture Therapy

Neutron capture therapy (NCT) stands as a transformative approach for precision oncology. The principle relies on tumor‐targeted isotopes, such as boron‐10 ( ¹⁰ B) and gadolinium‐157 ( ¹⁵⁷ Gd), for generating cytotoxic high energy particles upon thermal neutron irradiation. Compared to ¹⁰ B‐based NCT (BNCT), ¹⁵⁷ Gd offer unparalleled neutron capture cross‐section and MRI contrast capability, positioning it as a next‐generation theranostic candidate. Here, we developed hybrid polymeric‐gadolinium oxide core–shell nanoparticles (Gd ₂ O ₃ NPs) as an NCT platform. The Gd ₂ O ₃ NPs were synthesized from a series of poly(ethylene glycol)‐poly( L ‐aspartic acid) (PEG‐PAsp) block copolymers, aiming to optimize their biocompatibility, pharmacokinetics and tumor‐targeting capability. Suitable Gd ₂ O ₃ NP formulations showed sub‐100 nm size and excellent colloidal stability. Moreover, the Gd ₂ O ₃ NPs offered higher Gd loading and minimal Gd ³⁺ release. In a model of intractable pancreatic cancer, the Gd ₂ O ₃ NPs based on PEG‐PAsp having a PEG segment of 12 kDa and 20 Asp units exhibited highest therapeutic efficacy while maintaining systemic safety. This promising performance positions the Gd ₂ O ₃ NPs for further preclinical evaluation toward effective NCT treatments.