Dual-targeted therapy in HER2-positive breast cancer cells with the combination of carbon dots/HER3 siRNA and trastuzumab

Abstract

Dual -targeted therapy in HER2-positive breast cancer cells with the combination of carbon dots/HER3 siRNA and trastuzumab resulted in enhanced antitumor activity, which overcomes the resistance to trastuzumab monotherapy. Herein, we have developed branched polyethylenimine -functionalized carbon dot (BP-CD) nanocarriers, which exhibited efficient green fluorescent protein gene delivery and expression. The positively charged BP-CDs allowed for effective nucleic acid binding and displayed a high ly efficient small interfering RNA (siRNA)-mediated delivery targeting of cancer cells. The transfection of BP-CDs and HER3 siRNA complexes down-regulated HER3 protein expression and induced significant cell growth inhibition in BT-474 cells. BP-CDs/HER3 siRNA complexes induced cell death of BT-474 cells through G0/G1 cell cycle arrest and apoptosis. The combined treatment of BP-CDs/HER3 siRNA complexes and trastuzumab caused greater cell growth suppression in BT-474 cells when compared to either agent alone. The findings suggest that this dual -targeted therapy with the combination of BP-CDs/HER3 siRNA and trastuzumab represents a promising approach in breast cancer.

Microwave-Assisted Chitosan-Functionalized Graphene Oxide as Controlled Intracellular Drug Delivery Nanosystem for Synergistic Antitumour Activity

“…To study whether trastuzumab, an anti-HER2 monoclonal antibody, could improve the antitumour activity of equivalent amounts of adriamycin loaded on ChrGO, BT-474 cells were treated with trastuzumab alone or in combination with ChrGO/adriamycin. Treatment with trastuzumab alone produced a significant inhibition of BT-474 proliferation, which is consistent with a previous report [52]. The combined therapy with trastuzumab and ChrGO/adriamycin resulted in an enhanced cell growth inhibition effect, as shown by a reduction of 88.5% compared with a reduction of 54.5% with trastuzumab alone (5 μg/mL) and 59.5% with equivalent ChrGO/adriamycin alone (5 μg/mL) versus the negative control (Fig.…”

Highly Efficient MicroRNA Delivery Using Functionalized Carbon Dots for Enhanced Conversion of Fibroblasts to Cardiomyocytes

“…These results suggested that the surface passivation by PEI imparted a strong influence on the optical properties of N-CDs due to a change in the chemical functional groups. 47 Furthermore, the time-resolved fluorescence spectrum measured with an excitation at 350 nm showed that the fluorescence lifetime of N-CDs is 3.35 ns ( Figure S3 ).…”

“…The average hydrodynamic size of the BP-NCDs measured by DLS was 42.1 nm, which was slightly larger than that of the bare N-CDs (30.4 nm) due to the presence of the polymer PEI envelope ( Figure 2E ). 47 The surface charge of BP-NCDs reflects the capability of cationic-related carriers for nucleic acid delivery. 43 Zeta potential analysis demonstrated that the surface charge of N-CDs, branch PEI, and BP-NCDs was 7 mV, 10 mV, and 18 mV, respectively ( Figure 2F ).…”

“…The crystallinity of the bare N-CDs was examined by X-ray diffraction (XRD). The XRD pattern exhibited a broad peak between 20° and 35° 2 θ , which is attributed to the graphitic structure of carbon 47 ( Figure S1 ).

Figure 3 Compositional characterization of N-CDs and BP-NCDs.

…”

“…In other reports, fibroblast genes were gradually inhibited during the reprogramming of iCMs. 47–50 miRNA-133 direct target Snai1 3 ʹ UTR and restrain fiber mother cell surface markers such as COL1A1, COL1A2, POSTN, promote fibroblasts transition to the heart muscle cells. 21 With the reprogramming, the expression of COL1A1 decreases over time.…”