Black phosphorus quantum dots reverse the malignant potential and enhance chemosensitivity of human renal cell carcinoma cells by targeting histone deacetylase 1 signal pathway

Abstract

Targeted anti‐cancer therapy selectively inhibits the growth of malignant cells by interfering with cancer‐specific signaling pathways, and inflicts minimal toxicity to normal tissues. Here, the current study demonstrates black phosphorus quantum dots (BPQDs) can target histone deacetylase 1 (HDAC1), which is overexpressed in multiple tumors and involved in cancer progression. The BPQDs inhibit HDAC1 activity and impair HDAC1‐mediated deacetylation of the mitotic spindle protein Eg5 in human renal cell carcinoma (RCC) cells, thereby disrupting the mitotic spindle structure and stalling cell cycle progression. Since HDAC1 regulates multiple aspects of cancer progression, BPQDs can neutralize the malignant potential of cancer cells by suppressing their proliferation and migration, and inducing apoptosis. Further in vitro assays demonstrate BPQDs significantly increase the sensitivity of RCC cells to the clinical chemotherapeutic agent, paclitaxel (PTX). Moreover, animal experiments also indicate the combined approach with both BPQDs and PTX displays better efficacy than PTX alone. These findings demonstrate that BPQDs have potential applications in targeted anti‐cancer therapy and can be more effectively treated with chemotherapy.

Recent Advances in the Biological Responses to Nano-black Phosphorus: Understanding the Importance of Intrinsic Properties and Cell Types

“…The direct binding of nano-BPs to centrosome kinase polo-like kinase 1 (PLK1) induced the aggregation and deactivation of PLK1, subsequently resulting in the destruction of mitotic centrosomes. In addition, Shang et al found that BPDs could inhibit the activation of cancer-specific histone deacetylase 1 (HDAC1), which could mediate the deacetylation of the mitotic regulator Eg5 and induce the abnormal spindle assembly and mitotic arrest of human renal cell carcinoma (RCC) cells . Thereby, the malignant potential of RCC cells, regarding cellular proliferation and migration, was suppressed.…”

“…In addition, Shang et al found that BPDs could inhibit the activation of cancerspecific histone deacetylase 1 (HDAC1), which could mediate the deacetylation of the mitotic regulator Eg5 and induce the abnormal spindle assembly and mitotic arrest of human renal cell carcinoma (RCC) cells. 64 Thereby, the malignant potential of RCC cells, regarding cellular proliferation and migration, was suppressed.…”

“…Apoptosis is one of the major cell death modes caused by nanomaterials. BPDs, 64,85 BPNSs, 21,27,66,77 and polymer-functionalized nano-BPs 22,86,87 induced apoptotic cell death both in vitro and in vivo. Annexin V-FITC/PI staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assays are standard methods for detecting apoptotic cells at cellular and histological levels, respectively.…”