Vitamin B 12 ‐Functionalized Nanogels for pH‐, and Redox‐Responsive Doxorubicin Delivery

Rapidly proliferating cancer cells display an elevated demand for vitamin B 12 , rendering this bacterial‐derived cofactor an attractive targeting motif for nanotherapeutic drug delivery. Herein, we report a concise two‐step synthesis of a polymerizable 5′‐modified vitamin B 12 ‐monomer that enables the covalent integration of B 12 into pH‐ and redox‐responsive nanogels. The resulting nanogels efficiently encapsulate doxorubicin through electrostatic interactions between the cationic drug and the anionic nanogel network, while enabling stimuli‐responsive drug release under tumor‐relevant conditions. In vitro studies revealed that DOX@B 12 ‐nanogels retain potent antiproliferative activity against HT‐29 colorectal cancer cells (IC 50 = 0.878 ± 0.102 μM), while decreasing cytotoxicity toward healthy CCD 841 CoN cells by 34‐fold relative to non‐B 12 ‐functionalized control nanogels. These findings establish covalently engineered vitamin B 12 ‐nanogels as a promising platform for selective and stimuli‐responsive anticancer drug delivery.