Doxorubicin Intercalated Co‐Al Layered Double Hydroxide Nanocarrier With pH‐Responsive Controlled Release and Selective Melanoma Suppression: Toward Next‐Generation Nanotherapeutics

Abstract Clinical oncology grapples with persistent challenges, particularly the rapid onset of tumor resistance and the systemic limitations of conventional chemotherapeutics such as doxorubicin (Dox). Despite its potency, Dox suffers from poor solubility, non‐specific distribution, and severe toxicity, often compromising therapeutic efficacy. Addressing these obstacles, this study explores cobalt‐aluminium layered double hydroxides (Co‐Al LDHs) as smart nanocarriers for targeted melanoma therapy. Capitalizing on their tunable structure, high drug‐loading capacity, and biocompatibility, Co‐Al LDHs facilitate enhanced encapsulation, sustained release, and selective tumor accumulation of Dox. Density Functional Theory (DFT) analyses confirm robust molecular interactions between Dox and the LDH matrix, ensuring structural stability and favorable energetics for drug delivery. In vitro assays reveal significant cytotoxicity (≈80%) against melanoma cells and with minimal toxicity (≈8%) to normal muscle cells. Furthermore, in vivo evaluations using luciferase‐tagged B16‐F10 melanoma models demonstrate pronounced tumor inhibition and excellent systemic biocompatibility. Augmented by machine learning‐guided force field modelling, this platform also offers a predictive framework for engineering next‐generation nanotherapeutics. Together, these findings position Co‐Al LDHs as a promising frontier in nanomedicine, merging targeted delivery, controlled release, and computational precision to overcome current therapeutic barriers in melanoma treatment and beyond.