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.