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

Chien Tien Chen, Santosh Salunke, Tzu Tang Wei, Yen An Tang, Yi Ching Wang

研究成果: Article同行評審

3 引文 斯高帕斯(Scopus)

摘要

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 1H 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 (IC50) 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.

原文English
頁(從 - 到)2475-2489
頁數15
期刊ACS Applied Bio Materials
4
發行號3
DOIs
出版狀態Published - 2021 3月 15

All Science Journal Classification (ASJC) codes

  • 一般化學
  • 生物材料
  • 生物醫學工程
  • 生物化學(醫學)

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