Mechanically Responsive Organic–Inorganic Hybrid as Advanced Delivery Vehicle for Targeted Cancer Treatment

Abstract Clinical oncology grapples with a daunting challenge therapy resistance in tumors evolves rapidly, undermining treatment efficacy. Chemotherapy, while inducing specific cancer cell death, often falls short due to intrinsic cellular defences. This underscores the urgent need for precision and controlled therapeutic strategies. A breakthrough emerges in tumor targeted drug delivery through interlamellar surface modification of hydroxyl groups in pristine Li‐Al‐based layered double hydroxide (LDH). Grafting polyurethane (PU) onto LDH enhances its mechanical integrity, achieving an extraordinary elongation at break of 1230%. This exceptional flexibility enables the material to withstand substantial deformation, ensuring adaptability within dynamic physiological environments – critical for injectable and implantable drug carriers navigating complex biological structures. The polyurethane graft fine‐tunes the hydrophilic hydrophobic balance, orchestrating synchronized drug delivery. First principle density functional theory (DFT) analyses reveal intricate molecular interactions between the nanohybrid and doxorubicin (Dox)In vitro and in vivo studies, particularly in luciferase – expressing melanoma‐bearing mice, demonstrate remarkable biocompatibility and synergistic anticancer efficacy. Furthermore, an injectable hydrogel beneath the tumor site mitigates chemotherapy's toxic side effects by precisely regulating drug release. This pioneering nanohybrid heralds a new era in multifunctional nanomedicine, offering enhanced precision, stability, and patient compatibility, transforming the landscape of next generation cancer therapies.