Photoactive polymers-decorated Cu-Al layered double hydroxide hexagonal architectures: A potential non-viral vector for photothermal therapy and co-delivery of DOX/pCRISPR

Gene and drug co-delivery is considered a promising strategy in combination cancer therapy. In this study, we fabricated Cu-Al layered double hydroxide (LDH) decorated with nanoscale ortho-, meta-, and para-poly(phenylenediamine), and afterward, doxorubicin (DOX) was loaded into nanoparticles. Finally, LDH was wrapped with plasmid CRISPR (pCRISPR). The modified nanohexagonals had particle sizes of approximately less than 100 nm with drug uptake up to 62.3%. pH-responsive nanocarriers exhibited higher cargo release in an acidic environment (pH 5.5) compared to a neutral buffer of pH 7.4. CLSM analysis demonstrated internalization in MEF-7 and HEK-293 cells with high transfection efficiency, further confirming them as promising nanostructures in cargo delivery. Besides, the potential usage of the cell-imprinted technique in order to increase the interactions to the cells, and enhance the cellular internalizations/transfections were assessed and showed a considerable increase (up to 72%) in the cellular internalizations. LDH nanostructures displayed high biocompatibility against HEK-293 and PC12 cells after 24 and 48 h. While they had no significant impact on the viability of MCF-7 cells with the assistance of the cell-imprinted method, these non-viral vectors significantly reduced the viability of HT-29 cells, showing their anti-cancer activity. Ortho, meta, and para forms of the poly(phenylenediamine)s decorated on the surface of the LDH showed transfection efficiencies up to 29.1, 28.2, and 40.1%, respectively. Therefore, this study could be considered the highest record of the pCRISPR delivery using a composite substrate in the literature.