Engineered pH-responsive hydrazone-carboxylate complexes-encapsulated 2D matrices for cathepsin-mediated apoptosis in cancer.

Spurred by the current advancements in engineering various intelligent nanoparticle-based drug delivery systems, conjugation of drugs with the stimuli-responsive molecular switches has become one of the most efficient approaches to deliver a drug cargo in spatiotemporal controlled fashions. In this study, we fabricated an innovative pH-triggered hydrazone-carboxylate complex of doxorubicin (Dox), which was subsequently encapsulated in the layered double hydroxide (LDH) nanoparticles for effective cancer therapeutics. These two-dimensional (2D) biodegradable matrices efficiently delivered Dox by pH-triggered release in the acidic lysosomal environment and their subsequent escape to cytosol. Moreover, the delivered Dox molecules and high positively-charged surfaces of LDHs facilitated the cancer cell ablation via enhancing the cathepsins-mediated cell apoptosis assisted by free radical species generation. The critical advancements in the nanoparticle-based designs and substantial ablation of tumor cells through a free radical attack indicate that the designed pH-triggered drug composites can be used for efficient cancer therapeutics. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1184-1194, 2019.