Fluorescent Nanohybrids from ZnS/CdSe Quantum Dots Functionalized with Triantennary, N-Hydroxy-p-(4-arylbutanamido)benzamide/Gallamide Dendrons That Act as Inhibitors of Histone Deacetylase for Lung Cancer

Abstract

N-Hydroxy-p-(4-arylbutanamido)benzamides (HABAB) belong to one class of histone deacetylase inhibitors (HDACi), which regulate deacetylation of lysine residue's amino group in histone, which results in chromatin constriction. In addition, transcriptional knockdown of the genetic loci possessing the suppressor genes of tumor occurs. A tripodal, HABAB-capped gallamide dendron possessing thiol anchoring unit was prepared by the click method. The resultant hydrophilic dendritic unit was easily attached on the outer layer of CdSe/ZnS (i.e., core/shell type) quantum dots by thiolate−Zn interaction, as supported via 1 H NMR spectroscopic analysis of the conjugate with its original property of fluorescence. The resulting, water-miscible nanohybrid (nano-HTPB) which bore trivalent, peripheral HABABs as the HDACi was efficiently taken up by cells of lung cancer and transported into the nuclei of cells in 3 h, as confirmed by confocal microscopy analysis. The concentration levels of 50% inhibition (IC 50 ) after 48 h incubation of the nano-HTPB for A549 and H1299 lung cancer cell lines were 14 and 18 nM, respectively, which were about 150-fold lower than those of the parent HTPB analogues. Nano-HTPB at 20 nM induced the knockdown of cell cycle at second growth/mitosis (i.e., G2/M) transition, which eventually led to apoptosis of lung cancer cells, demonstrating that the nano-HTPB was much more potent in inhibiting lung cancer cell growth in a synergistic manner than the parent HTPB analogues. In addition, the dendritic HABAB-capped nanohybrid, nano-HTPB, is more effective than the parent HTPB analogues both in vitro and in vivo. Furthermore, the nano-HTPB is more effective than the parent HTPB to increase the acetylation level of proteins related to histone and nonhistone like p53 and tubulin. Our results confirmed that covalent encapsulation of quantum dots with peripheral, triantennary HDACis represented a feasible strategy for synergistic drug delivery with enhanced biological effects.

Recent advances in nanoparticle applications in respiratory disorders: a review

“…The thiolate–Zn interaction was also used to attach a histone deacetylase inhibitor, N -hydroxy- p -(4-arylbutanamido) benzamides, to the CdSe/ZnS QDs, which formed a water-miscible nanocarrier (20 nM, 48 h) that was employed to treat A549 and H1299 cancer cells. Investigation of the apoptosis cycle showed the breakdown of the cell cycle at the G2 - to - M transition while increasing the acetylation of p53 and tubulin, killing cancer cells, or inhibiting tumor growth synergistically and more efficiently than the free active agent ( Chen et al, 2021 ).…”

Expedient Azide–Alkyne Huisgen Cycloaddition Catalyzed by a Combination of VOSO4 with Cu(0) in Aqueous Media

“…Triazole heteroaromatics have widespread applications as synthetic templates, drug candidates, and natural product derivatives . Gycosyl-containing analogues bearing biological active cores and biomedicinal targeted designs have been booming interests both in both pharmaceutical industry and academic researches.…”