Recently, multidrug resistance (MDR) has become a major clinical chemotherapeutic burden that robustly diminishes the intracellular drug levels through various mechanisms. To overcome the doxorubicin (Dox) resistance in tumor cells, we designed a hierarchical nanohybrid system possessing copper-substituted mesoporous silica nanoparticles (Cu-MSNs). Further, Dox was conjugated to copper metal in the Cu-MSNs framework through a pH-sensitive coordination link, which is acutely sensitive to the tumor acidic environment (pH 5.0–6.0). In the end, the nanocarrier was coated with D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS), a P-gp inhibitor-entrenched compact liposome net for obstructing the drug efflux pump. Copper ions in the framework synergize the antitumor activity of Dox by enhancing the intracellular reactive oxygen species (ROS) levels through a Fenton-like reaction-mediated conversion of hydrogen peroxide. Furthermore, intracellularly generated ROS triggered the apoptosis by reducing the cellular as well as mitochondrial membrane integrity in MDR cells, which was confirmed by the mitochondrial membrane potential (MMP) measurement. The advancement of the design and critical improvement of cytotoxic properties through free radical attack demonstrate that the proposed hierarchical design can devastate the MDR for efficient cancer treatment.

Recently, layered double hydroxides (LDHs) have gathered vast interest due to overall positive charge, unique crystallinity, and biocompatibility for diverse applications. Despite the advantageous attributes, these hydrotalcites often result in several limitations concerning the application requirements, such as aggregation, as well as poor chemical and thermal stabilities, hindering their scale‐up progress and practical utilization. In addressing these issues, the recent advancements in the fabrication of intelligent LDHs nanocomposites based on organically (polymer/polyelectrolyte)‐modified and inorganic (metal)‐composited architectures are systematically presented. Initially, a brief note on the shortcomings in various fields and the chemistry of these pristine LDHs is given. Then, various synthetic strategies used to fabricate these emerging LDH nanocomposites are comprehensively emphasized, focusing on the advancements in their structure and applicability. In addition, the effects of various attractive physicochemical attributes of LDHs and their nanocomposite forms are discussed, including their applicability in adsorption, biomedicine, catalysis, energy, and environment‐related applications. In summary, this article is concluded with an outlook concerning the positioning of LDH‐based nanocomposites compared to other innovative materials, as well as the current challenges and future requirements for scale‐up.