A Porphyrinic Covalent Organic Polymer Nanoplatform for Carborane Delivery and Multifunctional Imaging-Guided Boron Neutron Capture Therapy of Breast Cancer.

Introduction: The advancement of boron neutron capture therapy (BNCT) is critically dependent on the development of efficient and traceable boron delivery agents. Methods: We designed and synthesized a porphyrin-based covalent organic polymer (T-COP) loaded with ortho-carborane (o-CB) and surface-functionalized with DSPE-PEG Results: The resulting nanocomposite exhibits a high boron content (28.82 wt%), excellent colloidal stability, and pronounced fluorescence derived from the porphyrin building blocks, thereby enabling real-time tracking. In vitro, T-COP@o-CB NPs have outstanding biocompatibility, efficient cellular uptake, and prolonged intracellular retention in 4T1 breast cancer cells. In vivo fluorescence imaging confirms effective tumor localization and retention following intratumoral injection. Most notably, in a subcutaneous breast cancer mouse model, the T-COP@o-CB NPs with thermal neutron irradiation achieve 73.04% tumor inhibition compared to all control groups, while exhibiting no significant systemic toxicity as validated by body weight monitoring and histopathological analysis. Conclusion: This work presents a promising theranostic platform that combines high boron loading, inherent self-imaging capability, and effective tumor inhibition, offering a new strategy for precise and enhanced BNCT.